Late-onset Schizophrenia-like Psychosis Research Articles

Clinical and psychopathological features of very late onset of schizophrenia-like psychosis

IntroductionVery late onset schizophrenia-like psychosis takes the 3rd place among late-life psychosis, after dementia and affective disorders associated psychosis. It’s still unknown the real place of this psychosis.Objectivesto investigate the clinical and psychopathological features and short-terms outcomes of late-onset schizophrenia and schizophrenia-like psychosisMethods45 patients, mean age 70,6 ±8,70 years, median age of manifestation psychosis - 68 [61; 75] years with late-onset schizophrenia (n=19, 42,2%), late-onset schizoaffective disorder (n=9, 20%), late-onset delusional disorder (n=7, 15,5%) and late-onset organic schizophrenia-like disorder (n=10, 22,3%) underwent clinical examination. Psychopathological, psychometric (PANSS, HAMD, CDSS, MoCA) and statistical methods were applied.Results3 clinical groups were allocated. The 1st group included 15 patients (33%) and was characterized with severe polymorphic psychotic symptoms, included catatonic and paraphrenic signs with mental disorganization. They had the highest score of PANSS (105,46±17,99, p=0,002) and the lowest score of MoCA (14,2±2,16, p=0,05) in compare with 2nd and 3rd groups. They also had symptoms of depression (CDSS 6,28±5,29), compared with the 3rd group (HAMD 21,00±5,92, p=0,05). In short-terms outcomes was formed negative symptoms and cognitive impairment with decreasing social and daily activity. The 2nd group (22 cases, 49%) included patients with prevalence of delusions of persecution, more rare auditory hallucinations and more often acoasms. They had medium score PANSS (90,22±16,79), with minimal cognitive declare (MoCA average score 20,33±4,27). The short-term outcomes were characterized with formation of residual positive and negative symptoms, that impact on daily and social activity. The 3rd group included 8 patients (8%) with prevalence of delusion symptoms, such as misidentification, persecutory and reference delusions, which were mood-congruent. They had medium PANSS score (89,75±18,90) with more severe depressive symptoms by HAMD scale in compare with 2nd group (22,00±10,00, p=0,07) and minimal cognitive declare (MoCA average score 25,00±1,00, p=0,05) in compare with 1st group. This group was characterized with high level of reduction of productive symptoms and restoration of premorbid social and daily activity in short-term outcomes.Conclusionsfeatures of clinical characteristics, including the nature and severity of cognitive impairment at the onset of disease, are significant for prognosis and outcomes of disease. The data obtained could be served for the development of personalized therapeutic approaches that take into account the syndromic features and course of late-onset psychosis.Disclosure of InterestNone Declared

LATE ONSET PSYCHOSIS – A CASE REPORT

Introduction – Late-onset psychosis is a disorder that is well-known but poorly understood, and it has emerged as an increasingly significant issue in geriatric patients. There is no clear information about whether this psychosis occurs for the first time at this age. Despite being underdiagnosed, this late-onset psychosis responds well to treatment. A bizarre, persecutory delusion is a hallmark symptom of late-onset schizophrenia. Methods – Presented the case of a 67-year-old woman who visited the Emergency Psychiatry Department complaining of persecutory thoughts, auditory hallucinations, and mild cognitive impairment. Results – This case report explores the diagnostic process and treatment options for very late-onset schizophrenia-like psychosis, including non-pharmacological and pharmacological approaches. Discuss – Psychotic symptoms can be caused by a variety of general medical conditions in elderly patients. It is necessary to rule out delirium, dementia, substance-related disorders, delusional disorder, and dissociative disorder before diagnosing Late-onset psychosis. A late-onset psychosis is not only challenging to diagnose but also to treat. Non-pharmacological treatments are the first option in managing late-life psychosis. It includes psycho-education for patients and their families, as well as cognitive behavior therapy (CBT). It is important to monitor for adverse reactions while administering medication, and the lowest dosage should be used to achieve short-term efficacy. In addition to antipsychotic medication, anticholinesterase inhibitors may also be effective in treating these patients. Conclusion: A careful observation and approach are required to make an etiological diagnosis of late-onset psychosis since there are no pathognomonic signs or symptoms. To achieve the best results, their efficacy and side effects should be monitored with regularity. Keywords: late-onset psychosis, dementia, schizophrenia.

Impact of loneliness and social isolation in older people in Japan

A decline in social functioning is a hallmark of dementia and is associated with worsening cognitive impairment, various behavioral and psychological symptoms, and caregiver burden. Since the feeling of loneliness is related to social function decline in people with mild cognitive impairment (MCI) and dementia, care for the social isolation that can cause loneliness is considered important in Japan, where the number of older people living alone is increasing.In addition to dementia, late-onset psychosis is also known to be affected by loneliness and social isolation. Psychosis that develops after age 60 and does not involve organic or affective disorders is defined as very late-onset schizophrenia-like psychosis (VLOSLP) and is known to be different in quality from psychosis that develops at a younger age. Social isolation has been reported as one of risk factors of VLOSLP, and although people with VLOSLP are independent in daily life, their social functioning is impaired in a way that is different from dementia due to their abnormalities in the content of thinking. Therefore, social isolation and decline of social functioning are also major problems for VLOSLP. Longitudinally, people with VLOSLP are more likely than the general older population to progress to dementia including Lewy body disease and Alzheimer’s disease subtypes. With the increasing importance of early diagnosis and intervention of these neurodegenerative diseases, identification and intervention of people with VLOSLP is a challenging but important topic.We are now investigating the use of robots with communication capabilities aiming to improve loneliness and social isolation of older people living alone with MCI, mild dementia and VLOSLP. On the other hand, we have found that loneliness in MCI and mild dementia does not necessarily correlate with social isolation status, such as living alone, indicating that loneliness and social isolation among older people requires further research.

Vascular Schizophrenia-like Psychosis in Older Adults.

The aims of this study were to analyze prevalence and severity of vascular risk factors in older patients referred to our clinic due to onset of Very Late-Onset Schizophrenia-Like Psychosis (VLOSLP) and to create a specific phenotype based on pathophysiological insight rather than age of onset. In a longitudinal study, 103 (M = 39, F = 64; mean age of 80.32 ± 7.65 years) patients were evaluated with cognitive, neuropsychiatric, and functional assessment scales. Blood concentration of hemoglobin (Hb), mean corpuscular volume (MCV), platelets, total protein test (TPT), creatinine, azotemia, glycemia, total cholesterol (TC), triglycerides (TG), uric acid (UA), sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), folate, vitamin B12 (Vit-B12), and homocysteine were measured. Presence/absence of tobacco use, alcohol consumption, psychoactive substance use, hypertension, hyperlipidemia, diabetes mellitus, and history of vascular disease were collected. Females were more apathetic than males (NPI-Apathy: p = 0.040). Males had a significantly higher level of Hb (p = 0.019) and UA (p = 0.001), and a lower level of platelets (p = 0.004) and Ca (p = 0.003), and used more tobacco (p = 0.046) and alcohol (p = 0.024) than females. Comparing patients < 80 and ≥80 years, we found differences in frequency of vascular risk factors among men (p = 0.027). In total, 102 patients were treated for psychosis (59.16% of them were using atypical antipsychotics). The results of this study could be useful for a progressive demonstration of the causal relationship between cardiac and cerebral vascular events and VLOSLP.

Late-onset psychose: een diagnostische en therapeutische uitdaging voor de clinicus

Late-onset psychosis: a diagnostic and therapeutic challenge for the clinician In clinical practice, doctors are frequently confronted with psychosis in the elderly (above 60 years). This symptomatology presents a diagnostic and therapeutic challenge for the clinician. Its cause may be primarily psychiatric or secondary to a somatic or neurological disorder. In this article, the case of an elderly woman presenting with typical partition delusions (the belief that something or someone exerts influence through impermeable structures) is described. This case illustrates the difficult differential diagnosis between primary psychiatric disorders and neurocognitive disorders with late-onset psychotic symptoms, as well as the discussion concerning the nosological classification of schizophrenia in the elderly population. At the end of the 20th century, the term ‘very late-onset schizophrenia-like psychosis’ was introduced for schizophrenia-like psychotic symptoms developing after the age of 60. To this day, the validity of the existence and the etiology of this subgroup of schizophrenia remain a matter of debate. Psychosocial interventions are the first step in the treatment of late-onset psychotic symptoms. The use of antipsychotics is reserved for persistent, severe and debilitating symptoms because of the many side effects in the elderly population. However, the symptoms are often intrusive and have a negative impact on general functioning, so that drug treatment is regularly used in clinical practice.

VERY LATE-ONSET SCHIZOPHRENIA-LIKE PSYCHOSIS: CASE REPORT AND CRITICAL LITERATURE REVIEW.

Late-life psychosis presents a challenge, wherein a wide range of differential diagnoses should be considered. Very late-onset schizophrenia-like psychosis (VLOSLP) is a nosological entity that remains a conundrum. We provide a comprehensive literature review on the neurobiological underpinnings of VLOSLP. We describe a case that typifies the clinical presentation of VLOSLP. Although not pathognomonic, certain features, namely the two-stage progression of psychotic episode, partition delusions, multimodal hallucinations, and absent formal thought disorder or negative symptoms, are quite suggestive of VLOSLP. Several medical causes that might cause late-life psychosis, including neuroinflammatory/immunology diseases, were ruled out. Neuroimaging revealed basal ganglia lacunar infarctions along with chronic white matter small-vessel ischemic disease. The diagnosis of VLOSLP is based on clinical evidence, and the aforementioned clinical features support this diagnostic hypothesis. This case adds to the growing body of evidence pertaining to the relevance of cerebrovascular risk factors in the pathophysiology of VLOSLP, alongside age-specific neurobiological processes. We hypothesized that microvascular brain lesions disrupt the frontal-subcortical circuitry and uncover other core neuropathological processes. Future research should focus on identifying a specific biomarker that would allow clinicians to more accurately diagnose VLOSLP, differentiate it from other overlapping clinical entities such as dementia or post-stroke psychosis, and provide a tailored treatment for the patient.

Characteristics of very late-onset schizophrenia-like psychosis classified with the biomarkers for Alzheimer's disease: a retrospective cross-sectional study.

We aimed to investigate the association between very late-onset schizophrenia-like psychosis (VLOSLP), a schizophrenia spectrum disorder with an onset of ≥60 years, and Alzheimer's disease (AD) using biomarkers. Retrospective cross-sectional study. Neuropsychology clinic of Osaka University Hospital in Japan. Thirty-three participants were classified into three groups: eight AD biomarker-negative VLOSLP (VLOSLP-AD), nine AD biomarker-positive VLOSLP (VLOSLP+AD), and sixteen amnestic mild cognitive impairment due to AD without psychosis (aMCI-P+AD) participants. Phosphorylated tau levels in the cerebrospinal fluid and 18F-Florbetapir positron emission tomography results were used as AD biomarkers. Several scales (e.g. the Mini-Mental State Examination (MMSE), Wechsler Memory Scale-Revised (WMS-R) Logical Memory (LM) I and II, and Neuropsychiatric Inventory (NPI)-plus) were conducted to assess clinical characteristics. Those in both VLOSLP-AD and +AD groups scored higher than those in aMCI-P+AD in WMS-R LM I. On the other hand, VLOSLP+AD participants scored in between the other two groups in the WMS-R LM II, with only VLOSLP-AD participants scoring significantly higher than aMCI-P+AD participants. There were no significant differences in sex distribution and MMSE scores among the three groups or in the subtype of psychotic symptoms between VLOSLP-AD and +AD participants. Four VLOSLP-AD and five VLOSLP+AD participants harbored partition delusions. Delusion of theft was shown in two VLOSLP-AD patients and five VLOSLP+AD patients. Some VLOSLP patients had AD pathology. Clinical characteristics were different between AD biomarker-positive and AD biomarker-negative VLOSLP, which may be helpful for detecting AD pathology in VLOSLP patients.

Approach to acute psychosis in older adults.

Approach to acute psychosis in older adults.

Biomarkers of neurodegeneration among patients with very late-onset schizophrenia-like psychosis: future implications.

Biomarkers of neurodegeneration among patients with very late-onset schizophrenia-like psychosis: future implications.

Pineal volume reduction as the neural correlate of very late-onset schizophrenia-like psychosis.

This study aimed to examine the relationship between pineal parenchymal volume (PPV) and schizophrenia-like psychosis (SLP) at the onset of ≥60 years. Exactly 21 patients with SLP, 50 with Alzheimer's disease (AD) with delusions of theft, and 35 with normal cognition were selected. The PPVs in patients with SLP and patients with AD with delusional theft were significantly lower than those in patients with normal cognition. Moreover, PPVs in nine patients with Very late-onset schizophrenia-like psychosis (VLOSLP) tended to be lower than that in patients with normal cognition. Thus, pineal volume reduction could be a neural correlate of VLOSLP.

Crossroad between current knowledge and new perspective of diagnostic and therapy of late-onset schizophrenia and very late-onset schizophrenia-like psychosis: An update.

Schizophrenia is a chronic, highly individualized disease with many symptoms that can occur with varying severity in different patients. Schizophrenia affects 1% of the population, but occurs in almost 20% of patients after 40 years of age. It should be noted that the next peak in the incidence of schizophrenia occurs at the age of 60 years, affects mostly females, and is closely associated with a high risk of developing memory disorders. Therefore, postadolescent schizophrenia includes two distinct groups of patients: those whose symptoms onset at the age of 45 or 60. The purposes of this literature review were as follows: (1) synthetically characterize the clinical manifestations of schizophrenia; (2) discuss difficulties in the diagnosis of schizophrenia, especially in patients over 40 years of age; (3) discuss the clinical utility of different classes of marker in diagnostic and differentiating schizophrenia from neurodegenerative diseases in elderly people; (4) discuss therapeutic options for schizophrenia, pharmacotherapy, and psychotherapy, emphasizing the role of caregivers of people with psychosis in therapy, in preadolescence and postadolescence schizophrenia. We have tried to primarily discuss the findings of original articles from the last 10 years with an indication of their clinical implications with the issues discussed in the various subsections. Moreover, despite many years of research, no specific, precise algorithm has been developed that can be used in clinical practice during the diagnosis of schizophrenia. For this reason, the diagnosis of schizophrenia is primarily based on an interview with the patient and his family, as well as on the experience of a psychiatrist. It also seems that schizophrenia treatment should be carried out holistically, including pharmacotherapy, psychotherapy, and the support of caregivers of patients who have this psychosis, which increases the achievement of therapeutic success. Finally, we must be aware of the difficulties in diagnosing schizophrenia in the elderly and the need to modify pharmacological treatment. Currently, no guidelines have been developed for the differentiation of negative symptoms in elderly patients with schizophrenia from amotivation/avolition/apathy symptoms in elderly patients with neurodegenerative disorders.

Characteristics of very late-onset schizophrenia-like psychosis as prodromal dementia with Lewy bodies: a cross-sectional study

BackgroundThis study aimed to identify cases of potential prodromal DLB in very late-onset schizophrenia-like psychosis (VLOSLP), using indicative biomarkers of dementia with Lewy bodies (DLB), and to evaluate the characteristics of psychosis as prodromal DLB.MethodsData of patients with VLOSLP without dementia and Parkinsonism, who underwent testing for at least one indicative biomarker of DLB, were retrospectively collected from the database of the psychiatry clinic at the Osaka University Hospital. Patients were divided into two groups based on the positive (VLOSLP+LB) and negative (VLOSLP–LB) results of the indicative biomarkers of DLB. Age, gender, cognitive battery scores, prevalence of each type of delusions and hallucinations, cerebral volume, and cerebral perfusion were compared between the two groups.ResultsEleven VLOSLP+LB and 23 VLOSLP–LB participants were enrolled. There were no significant differences in age, proportion of females, and MMSE scores between the two groups. The standardized score of the digit symbol substitution test was significantly lower in the VLOSLP+LB than in VLOSLP–LB group (6.9 [3.1] vs. 10.0 [2.7], p = 0.005). The prevalence of visual hallucinations was significantly higher in the VLOSLP+LB group than in the VLOSLP-LB group (81.8% vs. 26.1%, p = 0.003). Auditory hallucinations were prevalent in both groups (43.5% in VLOSLP–LB, and 45.5% in VLOSLP+LB). Among patients with auditory hallucinations, auditory hallucinations without coexistent visual hallucinations tended to be more prevalent in VLOSLP–LB (7 out of 10) than in VLOSLP+LB patients (1 out of 5). Although cerebral volume was not different in any region, cerebral perfusion in the posterior region, including the occipital lobe, was significantly lower in the VLOSLP+LB group.ConclusionsPsychomotor slowing, visual hallucinations, and reduced perfusion in the occipital lobe may be suggestive of prodromal DLB in VLOSLP patients, even though the clinical manifestations were similar in many respects between VLOSLP+LB and VLOSLP–LB. Although auditory hallucinations were prevalent in both groups, most patients in VLOSLP+LB complained of auditory hallucinations along with visual hallucinations. Future studies with a larger number of patients without selection bias are desirable.

Commentary: Futility in Psychiatry.

While other medical professions have grappled with end-of-life care, the areas of palliative psychiatry, and more particularly, futility in psychiatry, have not been thoroughly addressed. The 3 cases presented in this issue illustrate how patients can succumb to a medical condition while presenting with primary psychosis (a patient with treatment-resistant schizophrenia who starves himself), secondary psychosis (a patient with small cell cancer of the lung who develops psychotic symptoms in the context of a paraneoplastic neurological syndrome), or a factitious disorder (a patient with self-induced aplastic anemia from ingesting an oral chemotherapy agent). The descriptions of these challenging cases show how collaborative teamwork among psychiatric and medical treatment teams, including the provision of palliative care, can help patients and families, even if a fatal outcome appears certain.

Cognitive functions in late-onset psychosis

The review discusses cognitive functions in late-onset schizophrenia and very late-onset schizophrenia-like psychosis compared to cognition in normal aging, early-onset schizophrenia, and neurodegenerative diseases. The problem of the dynamics of the state of the cognitive functions in patients with late-onset schizophrenic psychoses is highlighted, and prospects for further research are discussed. Patients with late-onset schizophrenic psychosis are characterized by more pronounced cognitive deficits compared to normal aging, but less severe than cognitive changes observed in early-onset schizophrenia. Late-onset schizophrenia may be a heterogeneous condition in terms of cognitive dysfunction.

Brain Atrophy in First-Episode Psychosis of the Elderly Is Associated With Cognitive Decline.

Objective: To study brain atrophy and cognitive decline in elderly patients with first-episode psychosis (FEP).Methods: Elderly patients aged ≥ 60 years with FEP and onset of psychotic symptoms of ≤ 1 year remitted to the Helsinki University Hospital from December 2009 to December 2011 were included in the study. Diagnoses were made using DSM-IV-TR criteria. All patients had a brain scan, magnetic resonance imaging, or computed tomography. Cognitive performance was assessed using the Consortium to Establish a Registry for Alzheimer`s Disease cognitive test battery.Results: Of the 85 patients with FEP, 18 had very late-onset schizophrenia-like psychosis (VLOSP), 20 had delusional psychosis, 12 had depressive psychosis, and 35 had psychosis due to a general medical condition. Fifteen of the patients had an earlier history of schizophrenia not known at the time of admittance. These patients were analyzed separately. A vast majority of the FEP patients in all diagnostic groups exhibited signs of cortical atrophy, which was associated with early stage cognitive decline. Multivariate analyses showed that brain atrophy was associated with a decline in Mini-Mental State Examination, Clock Drawing Test, and verbal fluency scores in FEP patients.Conclusions: Brain atrophy is a frequent finding in elderly FEP patients and is associated with cognitive decline. Elderly patients with FEP should always undergo brain atrophy and cognition screening, as they may constitute an etiologic factor in such patients.

A Case Series of Very Late-onset Schizophrenia-like Psychosis: Is It a Dimension of Dementia?

Emerging research has shown that there may be a subset of patients who develop a first-break psychosis later in life when they are over 60 years of age. Very late-onset schizophrenia-like psychosis (VLOSLP) differs from early-onset schizophrenia in a few very important ways that lead us to believe that there may be a distinct pathologic process involved. We present 4 cases of females with psychotic symptoms that first appeared after the patients were 60 years of age. We conducted a literature review and found that our older adult psychiatric unit is not alone in struggling with diagnoses for these individuals. Some of these patients have a disease that will progress to a neurocognitive disorder, but a large group of others will remain cognitively intact. Fortunately, the treatment for both processes is very similar, but studies have shown that patients with VLOSLP will need significantly lower doses of antipsychotics compared with those with early-onset schizophrenia. It remains unclear if VLOSLP is a unique disorder, a prodrome to dementia, or a different condition that is not yet understood. Further research is needed to develop comprehensive treatment for patients with VLOSLP.

How to make a diagnosis in people with late-onset behavioral change

Behavioral Variant Frontotemporal Dementia is a neurodegenerative brain disorder associated with frontal, insular, and temporal lobar atrophy, characterized during its earliest stages by pervasive changes in personality and behavior, typically reported by the patient's caregivers. Behavioral symptoms include loss of empathy, disinhibition, compulsive behavior, and a shift towards impulsive and socially inappropriate behavior, most of which generally precede the onset of cognitive deficits. Whilst patients with bvFTD usually exhibit deficits on executive functions tests, other cognitive functions, such as visuospatial abilities and praxis, remain relatively well preserved early in the disease (although a subset of patients do present with significant episodic memory disturbance). In the absence of a biological marker, clinical diagnosis of bvFTD depends on the detection of these core neuropsychiatric features, making it difficult for practicing physicians to diagnose early bvFTD. Several factors make diagnosis of a possible behavioral variant of frontotemporal dementia (bvFTD) particularly challenging, especially the overlap of certain symptomatic dimensions such as apathy, disinhibition, depression, anhedonia, stereotyped behavior, and psychosis between bvFTD and several psychiatric disorders that appear in late adulthood. I will discuss the most frequent psychiatric conditions that can simulate early bvFTD symptoms, including late onset bipolar disorder, late onset schizophrenia-like psychosis, late onset depression, and attention deficit hyperactivity disorder in middle and older age.

Association between risk of dementia and very late-onset schizophrenia-like psychosis: a Swedish population-based cohort study.

Although the incidence of psychotic disorders among older people is substantial, little is known about the association with subsequent dementia. We aimed to examine the rate of dementia diagnosis in individuals with very late-onset schizophrenia-like psychosis (VLOSLP) compared to those without VLOSLP. Using Swedish population register data, we established a cohort of 15 409 participants with VLOSLP matched by age and calendar period to 154 090 individuals without VLOSLP. Participants were born between 1920 and 1949 and followed from their date of first International Classification of Diseases [ICD], Revisions 8-10 (ICD-8/9/10) non-affective psychotic disorder diagnosis after age 60 years old (or the same date for matched participants) until the end of follow-up (30th December 2011), emigration, death, or first recorded ICD-8/9/10 dementia diagnosis. We found a substantially higher rate of dementia in individuals with VLOSLP [hazard ratio (HR): 4.22, 95% confidence interval (95% CI) 4.05-4.41]. Median time-to-dementia-diagnosis was 75% shorter in those with VLOSLP (time ratio: 0.25, 95% CI 0.24-0.26). This association was strongest in the first year following VLOSLP diagnosis, and attenuated over time, although dementia rates remained higher in participants with VLOSLP for up to 20 years of follow-up. This association remained after accounting for potential misdiagnosis (2-year washout HR: 2.22, 95% CI 2.10-2.36), ascertainment bias (HR: 2.89, 95% CI 2.75-3.04), and differing mortality patterns between groups (subdistribution HR: 2.89, 95% CI 2.77-3.03). Our findings demonstrate that individuals with VLOSLP represent a high-risk group for subsequent dementia. This may be due to early prodromal changes for some individuals, highlighting the importance of ongoing symptom monitoring in people with VLOSLP.

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The aim of work: to present the analysis of current scientific publications devoted to the problem of late-onset schizophrenia. Material and methods: According to the key words «late schizophrenia», «late-onset schizophrenia» and «very late-onset schizophrenia-like psychosis» publications over the last two decades were chosen and analyzed in PubMed, MEDLINE and other scientific bases. Results: the publications are analyzed and the main stages of the historical development of the concept of late schizophrenia were described. Despite the lingering ambiguity of this concept, the possibility of both late manifestation of schizophrenia (after 40 years) and very late (after 60 years) was recognized. The review deals with the issues of classification, diagnosis, clinic and course of late schizophrenia. The results of modern paraclinical research methods are given. The relevance and prospects of further study of schizophrenic spectrum disorders in late age, their possible connection with organic changes in the brain is shown. Conclusion: improving the diagnosis of schizophrenic spectrum disorders in late life creates prospects for the development of effective methods for their prevention and treatment. The use of biological (paraclinical) examination methods will help develop a personalized approach to the management of patients with late schizophrenia, determine the severity of organic pathology and determine the prognosis for disease.

Amisulpride for very late-onset schizophrenia-like psychosis: the ATLAS three-arm RCT.

Very late-onset (aged ≥ 60 years) schizophrenia-like psychosis (VLOSLP) occurs frequently but no placebo-controlled, randomised trials have assessed the efficacy or risks of antipsychotic treatment. Most patients are not prescribed treatment. The study investigated whether or not low-dose amisulpride is superior to placebo in reducing psychosis symptoms over 12 weeks and if any benefit is maintained by continuing treatment thereafter. Treatment safety and cost-effectiveness were also investigated. Three-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial. Participants who received at least one dose of study treatment were included in the intention-to-treat analyses. Secondary care specialist old age psychiatry services in 25 NHS mental health trusts in England and Scotland. Patients meeting diagnostic criteria for VLOSLP and scoring > 30 points on the Brief Psychiatric Rating Scale (BPRS). Participants were randomly assigned to three arms in a two-stage trial: (1) 100 mg of amisulpride in both stages, (2) amisulpride then placebo and (3) placebo then amisulpride. Treatment duration was 12 weeks in stage 1 and 24 weeks (later reduced to 12) in stage 2. Participants, investigators and outcome assessors were blind to treatment allocation. Primary outcomes were psychosis symptoms assessed by the BPRS and trial treatment discontinuation for non-efficacy. Secondary outcomes were extrapyramidal symptoms measured with the Simpson-Angus Scale, quality of life measured with the World Health Organization's quality-of-life scale, and cost-effectiveness measured with NHS, social care and carer work loss costs and EuroQol-5 Dimensions. A total of 101 participants were randomised. Ninety-two (91%) participants took the trial medication, 59 (64%) completed stage 1 and 33 (56%) completed stage 2 treatment. Despite suboptimal compliance, improvements in BPRS scores at 12 weeks were 7.7 points (95% CI 3.8 to 11.5 points) greater with amisulpride than with placebo (11.9 vs. 4.2 points; p = 0.0002). In stage 2, BPRS scores improved by 1.1 point in those who continued with amisulpride but deteriorated by 5.2 points in those who switched from amisulpride to placebo, a difference of 6.3 points (95% CI 0.9 to 11.7 points; p = 0.024). Fewer participants allocated to the amisulpride group stopped treatment because of non-efficacy in stages 1 (p = 0.01) and 2 (p = 0.031). The number of patients stopping because of extrapyramidal symptoms and other side effects did not differ significantly between groups. Amisulpride treatment in the base-case analyses was associated with non-significant reductions in combined NHS, social care and unpaid carer costs and non-significant reductions in quality-adjusted life-years (QALYs) in both stages. Including patients who were intensive users of inpatient services in sensitivity analyses did not change the QALY result but resulted in placebo dominance in stage 1 and significant reductions in NHS/social care (95% CI -£8923 to -£122) and societal costs (95% CI -£8985 to -£153) for those continuing with amisulpride. The original recruitment target of 300 participants was not achieved and compliance with trial medication was highly variable. Low-dose amisulpride is effective and well tolerated as a treatment for VLOSLP, with benefits maintained by prolonging treatment. Potential adverse events include clinically significant extrapyramidal symptoms and falls. Trials should examine the longer-term effectiveness and safety of antipsychotic treatment in this patient group, and assess interventions to improve their appreciation of potential benefits of antipsychotic treatment and compliance with prescribed medication. Current Controlled Trials ISRCTN45593573 and EudraCT2010-022184-35. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 67. See the NIHR Journals Library website for further project information.