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International Review of Psychiatry... 2023Substance-induced psychosis is a secondary psychotic disorder resulting from drug abuse, characterized by one or more psychotic episodes. Drug-induced psychosis is... (Review)
Review
Substance-induced psychosis is a secondary psychotic disorder resulting from drug abuse, characterized by one or more psychotic episodes. Drug-induced psychosis is expected to resolve after a 30-day period of sobriety, however, individuals with this condition are more likely to develop severe drug addiction. Compared to primary psychosis, participants with drug-induced psychosis exhibit poorer family history of psychotic diseases, higher insight, fewer positive and negative symptoms, more depressive symptoms, and greater anxiety. Substance-induced psychosis is strongly associated with the emergence of bipolar illness or schizophrenia spectrum disorder, with an increased chance of developing schizophrenia at a younger age. Episodes of self-harm after substance-induced psychosis are strongly linked to an elevated likelihood of developing schizophrenia or bipolar disorder. Effective treatment involves ruling out emergencies, investigating underlying causes, and addressing acute intoxication and withdrawal. Management includes dynamic assessment, intervention, and vigilant monitoring in cases of suicidal behaviour. Antipsychotics may be used for short term, with gradual discontinuation when a person is in a stable condition. Relapse prevention strategies, both medication and non-medication-based, are crucial in long-term management. Conversion rates to schizophrenia or bipolar disorder can be as high as one in three individuals, with users and those with early-onset substance abuse at the highest risk.
Topics: Humans; Psychotic Disorders; Schizophrenia; Bipolar Disorder; Antipsychotic Agents; Substance-Related Disorders
PubMed: 38299647
DOI: 10.1080/09540261.2023.2261544 -
Journal of Psychopharmacology (Oxford,... Oct 2023Postpartum psychosis (PPP) is a psychiatric emergency that generally warrants acute inpatient care. PPP is marked by the sudden onset of affective and psychotic symptoms... (Review)
Review
BACKGROUND
Postpartum psychosis (PPP) is a psychiatric emergency that generally warrants acute inpatient care. PPP is marked by the sudden onset of affective and psychotic symptoms with a rapid deterioration in mental state. Evidence suggests that PPP is a discrete disorder on the bipolar disorder spectrum with a distinct treatment profile and prognosis.
METHODS
We conducted a PubMed database search for various terms involving PPP and its treatment and included peer-reviewed articles published in English.
OBJECTIVE
To provide a treatment algorithm for the management of PPP based on available evidence.
RESULTS
Pharmacological therapy is the mainstay of PPP management in the acute phase. Evidence points to a combination of antipsychotics and lithium in the acute treatment of PPP. Electroconvulsive therapy can offer a rapid treatment response where required. Lithium appears to have the best evidence for relapse prevention and prophylaxis in PPP. Psychoeducation is essential and psychosocial interventions used in bipolar disorder may be effective in PPP.
CONCLUSION
Early detection and prompt treatment with antipsychotics and lithium, followed by maintenance treatment with lithium, is associated with a favourable prognosis in PPP.
Topics: Female; Humans; Lithium; Psychotic Disorders; Bipolar Disorder; Antipsychotic Agents; Postpartum Period; Algorithms
PubMed: 37515460
DOI: 10.1177/02698811231181573 -
International Psychogeriatrics Jan 2024Several etiologies can underlie the development of late-onset psychosis, defined by first psychotic episode after age 40 years. Late-onset psychosis is distressing to... (Review)
Review
BACKGROUND
Several etiologies can underlie the development of late-onset psychosis, defined by first psychotic episode after age 40 years. Late-onset psychosis is distressing to patients and caregivers, often difficult to diagnose and treat effectively, and associated with increased morbidity and mortality.
METHODS
The literature was reviewed with searches in Pubmed, MEDLINE, and the Cochrane library. Search terms included "psychosis," "delusions," hallucinations," "late onset," "secondary psychoses," "schizophrenia," bipolar disorder," "psychotic depression," "delirium," "dementia," "Alzheimer's," "Lewy body," "Parkinson's, "vascular dementia," and "frontotemporal dementia." This overview covers the epidemiology, clinical features, neurobiology, and therapeutics of late-onset psychoses.
RESULTS
Late-onset schizophrenia, delusional disorder, and psychotic depression have unique clinical characteristics. The presentation of late-onset psychosis requires investigation for underlying etiologies of "secondary" psychosis, which include neurodegenerative, metabolic, infectious, inflammatory, nutritional, endocrine, and medication toxicity. In delirium, psychosis is common but controlled evidence is lacking to support psychotropic medication use. Delusions and hallucinations are common in Alzheimer's disease, and hallucinations are common in Parkinson's disease and Lewy body dementia. Psychosis in dementia is associated with increased agitation and a poor prognosis. Although commonly used, no medications are currently approved for treating psychosis in dementia patients in the USA and nonpharmacological interventions need consideration.
CONCLUSION
The plethora of possible causes of late-onset psychosis requires accurate diagnosis, estimation of prognosis, and cautious clinical management because older adults have greater susceptibility to the adverse effects of psychotropic medications, particularly antipsychotics. Research is warranted on developing and testing efficacious and safe treatments for late-onset psychotic disorders.
Topics: Humans; Alzheimer Disease; Delirium; Hallucinations; Psychotic Disorders; Psychotropic Drugs; Schizophrenia
PubMed: 36866576
DOI: 10.1017/S1041610223000157 -
Journal of Child Psychology and... Jul 2023Psychotic symptoms, including hallucinations, delusions, and disorganized thinking and behaviors, are the hallmarks of schizophrenia; but may also present in the context... (Review)
Review
Psychotic symptoms, including hallucinations, delusions, and disorganized thinking and behaviors, are the hallmarks of schizophrenia; but may also present in the context of other psychiatric and medical conditions. Many children and adolescents describe psychotic-like experiences, which can be associated with other types of psychopathology and past experiences (e.g., trauma, substance use, and suicidality). However, most youth reporting such experiences do not have, nor will ever develop, schizophrenia or another psychotic disorder. Accurate assessment is critical because these different presentations have different diagnostic and treatment implications. For this review, we focus primarily on the diagnosis and treatment of early onset schizophrenia. In addition, we review the development of community-based first-episode psychosis programming, and the importance of early intervention and coordinated care.
Topics: Adolescent; Child; Humans; Psychotic Disorders; Schizophrenia; Hallucinations; Suicidal Ideation; Psychopathology; Delusions
PubMed: 36878476
DOI: 10.1111/jcpp.13777 -
Nature Reviews. Neurology Jan 2024Schizophrenia is a leading cause of global disability. Current pharmacotherapy for the disease predominantly uses one mechanism - dopamine D2 receptor blockade - but... (Review)
Review
Schizophrenia is a leading cause of global disability. Current pharmacotherapy for the disease predominantly uses one mechanism - dopamine D2 receptor blockade - but often shows limited efficacy and poor tolerability. These limitations highlight the need to better understand the aetiology of the disease to aid the development of alternative therapeutic approaches. Here, we review the latest meta-analyses and other findings on the neurobiology of prodromal, first-episode and chronic schizophrenia, and the link to psychotic symptoms, focusing on imaging evidence from people with the disorder. This evidence demonstrates regionally specific neurotransmitter alterations, including higher glutamate and dopamine measures in the basal ganglia, and lower glutamate, dopamine and γ-aminobutyric acid (GABA) levels in cortical regions, particularly the frontal cortex, relative to healthy individuals. We consider how dysfunction in cortico-thalamo-striatal-midbrain circuits might alter brain information processing to underlie psychotic symptoms. Finally, we discuss the implications of these findings for developing new, mechanistically based treatments and precision medicine for psychotic symptoms, as well as negative and cognitive symptoms.
Topics: Humans; Schizophrenia; Dopamine; Neurochemistry; Psychotic Disorders; Glutamic Acid
PubMed: 38110704
DOI: 10.1038/s41582-023-00904-0 -
Schizophrenia Research Feb 2024With new data about different aspects of schizophrenia being continually generated, it becomes necessary to periodically revisit exactly what we know. Along with a need... (Review)
Review
With new data about different aspects of schizophrenia being continually generated, it becomes necessary to periodically revisit exactly what we know. Along with a need to review what we currently know about schizophrenia, there is an equal imperative to evaluate the construct itself. With these objectives, we undertook an iterative, multi-phase process involving fifty international experts in the field, with each step building on learnings from the prior one. This review assembles currently established findings about schizophrenia (construct, etiology, pathophysiology, clinical expression, treatment) and posits what they reveal about its nature. Schizophrenia is a heritable, complex, multi-dimensional syndrome with varying degrees of psychotic, negative, cognitive, mood, and motor manifestations. The illness exhibits a remitting and relapsing course, with varying degrees of recovery among affected individuals with most experiencing significant social and functional impairment. Genetic risk factors likely include thousands of common genetic variants that each have a small impact on an individual's risk and a plethora of rare gene variants that have a larger individual impact on risk. Their biological effects are concentrated in the brain and many of the same variants also increase the risk of other psychiatric disorders such as bipolar disorder, autism, and other neurodevelopmental conditions. Environmental risk factors include but are not limited to urban residence in childhood, migration, older paternal age at birth, cannabis use, childhood trauma, antenatal maternal infection, and perinatal hypoxia. Structural, functional, and neurochemical brain alterations implicate multiple regions and functional circuits. Dopamine D-2 receptor antagonists and partial agonists improve psychotic symptoms and reduce risk of relapse. Certain psychological and psychosocial interventions are beneficial. Early intervention can reduce treatment delay and improve outcomes. Schizophrenia is increasingly considered to be a heterogeneous syndrome and not a singular disease entity. There is no necessary or sufficient etiology, pathology, set of clinical features, or treatment that fully circumscribes this syndrome. A single, common pathophysiological pathway appears unlikely. The boundaries of schizophrenia remain fuzzy, suggesting the absence of a categorical fit and need to reconceptualize it as a broader, multi-dimensional and/or spectrum construct.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Schizophrenia; Psychotic Disorders; Bipolar Disorder; Autistic Disorder; Brain
PubMed: 38086109
DOI: 10.1016/j.schres.2023.11.015 -
JAMA Psychiatry Nov 2023Episodes of substance-induced psychosis are associated with increased risk of developing a schizophrenia spectrum disorder. However, there are limited data on the...
IMPORTANCE
Episodes of substance-induced psychosis are associated with increased risk of developing a schizophrenia spectrum disorder. However, there are limited data on the transition risk for substance use without psychosis.
OBJECTIVES
To quantify the risk of transition to schizophrenia spectrum disorder following an incident emergency department (ED) visit for (1) substance-induced psychosis and (2) substance use without psychosis and to explore factors associated with transition.
DESIGN, SETTINGS, AND PARTICIPANTS
A population-based retrospective cohort study (January 2008 to March 2022) of all individuals, aged 14 to 65 years, in Ontario, Canada, with no history of a psychotic disorder. Individuals with incident ED visits for substance use with and without psychosis were compared with members of the general population.
MAIN OUTCOMES AND MEASURES
Transition to schizophrenia spectrum disorder using a chart-validated algorithm. Associations between ED visits for substance use and subsequent transition were estimated using cause-specific hazard models.
RESULTS
The study included 9 844 497 individuals, aged 14 to 65 years (mean [SD] age, 40.2 [14.7] years; 50.2% female) without a history of psychosis. There were 407 737 individuals with an incident ED visit for substance use, of which 13 784 (3.4%) ED visits were for substance-induced psychosis. Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio [aHR], 163.2; 95% CI, 156.1-170.5) increased risk of transitioning, relative to the general population (3-year risk, 18.5% vs 0.1%). Individuals with an ED visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%), but incurred more than 3 times the absolute number of transitions (9969 vs 3029). Cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2). Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger compared with older individuals, particularly for cannabis use.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that ED visits for substance use were associated with an increased risk of developing a schizophrenia spectrum disorder. Although substance-induced psychoses had a greater relative transition risk, substance use without psychosis was far more prevalent and resulted in a greater absolute number of transitions. Several factors were associated with higher transition risk, with implications for counseling and early intervention.
Topics: Humans; Male; Female; Adult; Schizophrenia; Cohort Studies; Retrospective Studies; Psychotic Disorders; Substance-Related Disorders; Cannabis; Hallucinogens; Emergency Service, Hospital; Ontario
PubMed: 37755727
DOI: 10.1001/jamapsychiatry.2023.3582 -
Pharmacological Reports : PR Dec 2023Psychedelics are compounds acting by serotonin 5-hydroxytryptamine (5-HT) receptor activation and induce several behavioral responses. They are of special interest... (Review)
Review
Psychedelics are compounds acting by serotonin 5-hydroxytryptamine (5-HT) receptor activation and induce several behavioral responses. They are of special interest because of their positive effects on neuropsychiatric disorders (depression and posttraumatic stress disorder). However, several findings revealed that some psychedelic actions are similar to symptoms observed in schizophrenia (psychosis, sensorimotor gating impairments, attention, and working memory deficits) which might limit their clinical applications. Psychedelics activate some neurotransmitters, i.e., serotonergic, and glutamatergic, that are also impaired in schizophrenia. Therefore, the neurobiological background of psychedelics and schizophrenia is partially similar. Another important aspect to discuss is the perspective of using psychedelics in schizophrenia therapy. Postmortem studies showed a loss of synapses in schizophrenia, and the positive effects of psychedelics on neuroplasticity (synaptogenesis, neurogenesis, and neuritogenesis) might be essential in the context of schizophrenia therapy. However, because of psychedelics' psychotic action, the recommended doses of psychedelics in schizophrenia treatment are not established, and subpsychedelic dosing or microdosing are considered. Exploratory studies are needed to determine the tolerability of treatment and appropriate dosing regimen. Another therapeutic option is using non-hallucinogenic psychedelic analogs that also induce neuroplastic outcomes but do not have psychotogenic effects. Further preclinical and clinical studies are needed to recognize the potential effectiveness of 5-HT agonists in schizophrenia therapy.
Topics: Humans; Hallucinogens; Schizophrenia; Serotonin; Psychotic Disorders; Memory, Short-Term
PubMed: 37899392
DOI: 10.1007/s43440-023-00546-5 -
The Lancet. Psychiatry Nov 2023Maintenance antipsychotic medication is recommended for people with schizophrenia or recurrent psychosis, but the adverse effects are burdensome, and evidence on... (Randomized Controlled Trial)
Randomized Controlled Trial
Antipsychotic dose reduction and discontinuation versus maintenance treatment in people with schizophrenia and other recurrent psychotic disorders in England (the RADAR trial): an open, parallel-group, randomised controlled trial.
BACKGROUND
Maintenance antipsychotic medication is recommended for people with schizophrenia or recurrent psychosis, but the adverse effects are burdensome, and evidence on long-term outcomes is sparse. We aimed to assess the benefits and harms of a gradual process of antipsychotic reduction compared with maintenance treatment. Our hypothesis was that antipsychotic reduction would improve social functioning with a short-term increase in relapse.
METHODS
RADAR was an open, parallel-group, randomised trial done in 19 National Health Service Trusts in England. Participants were aged 18 years and older, had a diagnosis of recurrent, non-affective psychotic disorder, and were prescribed an antipsychotic. Exclusion criteria included people who had a mental health crisis or hospital admission in the past month, were considered to pose a serious risk to themselves or others by a treating clinician, or were mandated to take antipsychotic medication under the Mental Health Act. Through an independent, internet-based system, participants were randomly assigned (1:1) to gradual, flexible antipsychotic reduction, overseen by treating clinicians, or to maintenance. Participants and clinicians were aware of treatment allocations, but assessors were masked to them. Follow-up was for 2 years. Social functioning, assessed by the Social Functioning Scale, was the primary outcome. The principal secondary outcome was severe relapse, defined as requiring admission to hospital. Analysis was done blind to group identity using intention-to-treat data. The trial is completed and has been registered with ISRCTN registry (ISRCTN90298520) and with ClinicalTrials.gov (NCT03559426).
FINDINGS
4157 people were screened, of whom 253 were randomly allocated, including 168 (66%) men, 82 (32%) women, and 3 (1%) transgender people, with a mean age of 46 years (SD 12, range 22-79). 171 (67%) participants were White, 52 (21%) were Black, 16 (6%) were Asian, and 12 (5%) were of other ethnicity. The median dose reduction at any point during the trial was 67% in the reduction group and zero in the maintenance group; at 24 months it was 33% versus zero. At the 24-month follow-up, we assessed 90 of 126 people assigned to the antipsychotic dose reduction group and 94 of 127 assigned to the maintenance group, finding no difference in the Social Functioning Scale (β 0·19, 95% CI -1·94 to 2·33; p=0·86). There were 93 serious adverse events in the reduction group affecting 49 individuals, mainly comprising admission for a mental health relapse, and 64 in the maintenance group, relating to 29 individuals.
INTERPRETATION
At 2-year follow-up, a gradual, supported process of antipsychotic dose reduction had no effect on social functioning. Our data can help to inform decisions about the use of long-term antipsychotic medication.
FUNDING
National Institute for Health Research.
Topics: Male; Female; Humans; Young Adult; Adult; Middle Aged; Aged; Schizophrenia; Antipsychotic Agents; Drug Tapering; State Medicine; Treatment Outcome; Psychotic Disorders; England; Recurrence
PubMed: 37778356
DOI: 10.1016/S2215-0366(23)00258-4 -
Psychiatry Research Sep 2023Schizophrenia (SCZ), a serious mental disorder, is one of the leading causes of disease burden worldwide. Exosomes, as a natural nanocarrier, are able to cross the... (Review)
Review
Schizophrenia (SCZ), a serious mental disorder, is one of the leading causes of disease burden worldwide. Exosomes, as a natural nanocarrier, are able to cross the blood-brain barrier (BBB) and play a key bridging role in central nervous system (CNS) communication, participating in important physiological processes such as neural regeneration, prominent plasticity, axonal support, and neuroinflammation. In recent years, exosomes have received widespread attention in the field of neurodegenerative diseases and mental disorders, especially Alzheimer's disease. However, there are few reviews on exosomes and SCZ. Therefore, we conducted a literature search in PubMed and Web of Science using the following search terms: "schizophrenia", "mental disorder", "central system", "exosome", "extracellular vesicles" to identify publications from January 2010 to December 2022. Our review summarized exosomes secreted by different cell types in the CNS and the double-edged role of exosomes in the development of SCZ, and discussed their future potential as biomarkers and therapeutic targets. In conclusion, this article provides an up-to-date overview of the current research on the involvement of exosomes in SCZ, while also highlighting the challenges that are currently faced in this field.
Topics: Humans; Schizophrenia; Exosomes; Alzheimer Disease; Blood-Brain Barrier; Psychotic Disorders
PubMed: 37536144
DOI: 10.1016/j.psychres.2023.115394