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Psychological Medicine Oct 2022Non-affective psychotic disorders have been associated with an increased risk of developing dementia. However, research in this area remains limited, highlighting the... (Review)
Review
Non-affective psychotic disorders have been associated with an increased risk of developing dementia. However, research in this area remains limited, highlighting the need for an up-to-date systematic review and meta-analysis of the evidence. We aimed to systematically review and quantify the risk of dementia associated with psychotic disorders. We searched four electronic databases for longitudinal studies investigating non-affective psychotic disorders and subsequent dementia. We used random-effects meta-analyses to pool estimates across studies and assessed risk of bias for each study. Non-affective psychotic disorders were associated with increased risk of all-cause dementia; pooled risk ratio (RR) = 2.52, 95% confidence interval (CI) (1.67-3.80), = 99.7%, = 12,997,101; 11 studies, with high heterogeneity between studies. Subgroup analyses indicated stronger associations in studies with shorter follow-up periods, conducted in non-European countries, published after 2020, and where ≥60% of the sample were female. The risk was higher in people aged <60 years at baseline, in typical and late-onset psychotic disorders versus very late-onset psychosis, in broader psychotic disorders vs schizophrenia, and in prospective vs retrospective studies. Associations remained after excluding low quality studies (pooled RR = 2.50, 95% CI (1.71-3.68), = 99.0%). Our review finds a substantial association between psychotic disorders and subsequent dementia. Our findings indicate that psychotic disorders are a potentially modifiable risk factor for dementia and suggest that individuals with psychotic disorders need to be closely monitored for cognitive decline in later life. Further research is needed to investigate the mechanisms underlying the association between psychotic disorders and dementia.
PubMed: 36200264
DOI: 10.1017/S0033291722002781 -
Expert Opinion on Drug Safety Mar 2021: A century-long history in 8-aminoquinolines, the only anti-malaria drug class preventing malaria relapse, has resulted in the approval of tafenoquine by the U.S. Food... (Meta-Analysis)
Meta-Analysis
: A century-long history in 8-aminoquinolines, the only anti-malaria drug class preventing malaria relapse, has resulted in the approval of tafenoquine by the U.S. Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA) and to date registration in Brazil and Thailand. Tafenoquine is an alternative anti-relapse treatment for vivax malaria and malaria prophylaxis. It should not be given in pregnancy, during lactation of infants with glucose-6-phosphate dehydrogenase (G6PD) unknown or deficient status, and in those with G6PD deficiency or psychiatric illness.: This systematic review assesses tafenoquine associated adverse events in English-language, human clinical trials. Meta-analysis of commonly reported adverse events was conducted and grouped by comparison arms.: Tafenoquine, either for radical cure or prophylaxis, is generally well tolerated in adults. There is no convincing evidence for neurologic, ophthalmic, and cardiac toxicities. Psychotic disorder which has been attributed to higher doses is a contraindication for the chemoprophylaxis indication and psychiatric illness is a warning for the radical cure indication. Pregnancy assessment and quantitative G6PD testing are required. The optimal radical curative regimen including the tafenoquine dose along with its safety for parts of Southeast Asia, South America, and Oceania needs further assessment.
Topics: Adult; Aminoquinolines; Animals; Antimalarials; Dose-Response Relationship, Drug; Glucosephosphate Dehydrogenase Deficiency; Humans; Malaria, Vivax; Mental Disorders
PubMed: 33306921
DOI: 10.1080/14740338.2021.1859476 -
Focus (American Psychiatric Publishing) Apr 2023Suicide is a public health crisis. We conducted a systematic review and meta-analysis of the effects of psychopharmacologic and somatic therapies on suicide risk.
BACKGROUND
Suicide is a public health crisis. We conducted a systematic review and meta-analysis of the effects of psychopharmacologic and somatic therapies on suicide risk.
METHODS
A systematic search of MEDLINE for studies evaluating the effects of pharmacologic (excluding antidepressants) or somatic interventions on suicide risk was conducted. Studies were included if they used a comparison group, reported on suicide death, assessed a psychopharmacological or somatic intervention, and included adults. Study quality was assessed using the Newcastle-Ottawa scale. Fifty-seven studies were included from 2940 reviewed citations.
RESULTS
In bipolar disorder, lithium was associated with a reduction in the odds of suicide compared to active controls (odds ratio [OR] = .58, = .005; = 12) and compared to placebo/no lithium (OR = .46, = .009; = 9). In mixed diagnostic samples, lithium was associated with a reduction in the odds of suicide compared to placebo/no lithium (OR = .27, < .001; = 12), but not compared to active controls (OR = .89, = .468; = 7). In psychotic disorders, clozapine was associated with a reduction in the odds of suicide (OR = .46, = .007; = 7). Associations between suicide death and electroconvulsive therapy (OR = .77, = .053; = 11), non-clozapine antipsychotics in bipolar disorder (OR = .73, = .090; = 6) and antipsychotics in psychotic disorders (OR = .39, = .069; = 6) were not significant. There was no consistent relationship between antiepileptic mood stabilizers and suicide. There were insufficient studies to meta-analyze associations of suicide risk with vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, or transcranial direct current stimulation.
CONCLUSION
Lithium and clozapine have consistent data supporting protective effects against suicide in certain clinical contexts.Reprinted from with permission from John Wiley and Sons. Copyright © 2022.
PubMed: 37201149
DOI: 10.1176/appi.focus.23021006 -
The Cochrane Database of Systematic... May 2015Delusional disorder is commonly considered to be difficult to treat. Antipsychotic medications are frequently used and there is growing interest in a potential role for... (Review)
Review
BACKGROUND
Delusional disorder is commonly considered to be difficult to treat. Antipsychotic medications are frequently used and there is growing interest in a potential role for psychological therapies such as cognitive behavioural therapy (CBT) in the treatment of delusional disorder.
OBJECTIVES
To evaluate the effectiveness of medication (antipsychotic medication, antidepressants, mood stabilisers) and psychotherapy, in comparison with placebo in delusional disorder.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (28 February 2012).
SELECTION CRITERIA
Relevant randomised controlled trials (RCTs) investigating treatments in delusional disorder.
DATA COLLECTION AND ANALYSIS
All review authors extracted data independently for the one eligible trial. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis with a fixed-effect model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again with a fixed-effect model. We assessed the risk of bias of the included study and used the GRADE approach to rate the quality of the evidence.
MAIN RESULTS
Only one randomised trial met our inclusion criteria, despite our initial search yielding 141 citations. This was a small study, with 17 people completing a trial comparing CBT to an attention placebo (supportive psychotherapy) for people with delusional disorder. Most participants were already taking medication and this was continued during the trial. We were not able to include any randomised trials on medications of any type due to poor data reporting, which left us with no usable data for these trials. For the included study, usable data were limited, risk of bias varied and the numbers involved were small, making interpretation of data difficult. In particular there were no data on outcomes such as global state and behaviour, nor any information on possible adverse effects.A positive effect for CBT was found for social self esteem using the Social Self-Esteem Inventory (1 RCT, n = 17, MD 30.5, CI 7.51 to 53.49, very low quality evidence), however this is only a measure of self worth in social situations and may thus not be well correlated to social function. More people left the study early if they were in the supportive psychotherapy group with 6/12 leaving early compared to 1/6 from the CBT group, but the difference was not significant (1 RCT, n = 17, RR 0.17, CI 0.02 to 1.18, moderate quality evidence). For mental state outcomes the results were skewed making interpretation difficult, especially given the small sample.
AUTHORS' CONCLUSIONS
Despite international recognition of this disorder in psychiatric classification systems such as ICD-10 and DSM-5, there is a paucity of high quality randomised trials on delusional disorder. There is currently insufficient evidence to make evidence-based recommendations for treatments of any type for people with delusional disorder. The limited evidence that we found is not generalisable to the population of people with delusional disorder. Until further evidence is found, it seems reasonable to offer treatments which have efficacy in other psychotic disorders. Further research is needed in this area and could be enhanced in two ways: firstly, by conducting randomised trials specifically for people with delusional disorder and, secondly, by high quality reporting of results for people with delusional disorder who are often recruited into larger studies for people with a variety of psychoses.
Topics: Cognitive Behavioral Therapy; Humans; Psychotherapy; Randomized Controlled Trials as Topic; Schizophrenia, Paranoid; Self Concept
PubMed: 25997589
DOI: 10.1002/14651858.CD009785.pub2 -
Dementia and Geriatric Cognitive... 2022Homicide by older offenders is rare and devastating. It likely occurs due to a complex interaction of personal, social, and environmental factors. Dementia is a...
BACKGROUND
Homicide by older offenders is rare and devastating. It likely occurs due to a complex interaction of personal, social, and environmental factors. Dementia is a progressive neurological condition which may amplify behavioural disturbances such as aggression. This systematic review aims to evaluate the factors associated with homicide committed by people with dementia in order to inform clinical practice.
SUMMARY
MEDLINE, PsychINFO, Embase, and PubMed databases were searched in accordance with PRISMA guidelines for empirical studies examining the characteristics and circumstances of people with dementia who committed homicides. Data on factors associated with the homicide were extracted and the quality of each study rated using standardized criteria. A total of 499 papers were screened and thirteen studies met the inclusion criteria. Study design included case reports (seven studies), case series (four studies), and two retrospective cohort studies, indicative of low levels of evidence. Sample sizes were 1-70. Study findings were predominantly descriptive. Quality ratings ranged from 50 to 100%. Factors associated with disinhibition such as dysexecutive syndrome, alcohol use, and delirium may predispose to severe impulsive aggression. Psychosis and personality pathology appeared to influence targeted assaults resulting in homicide by people with dementia. Victim vulnerability was also a key element.
KEY MESSAGES
The current evidence examining risk factors for homicide committed by people with dementia is limited. However, there are common characteristics reported in these descriptive studies including psychiatric factors and cognitive states causing disinhibition. Recommendations for clinical practice include early assessment of older people with dementia and changed behaviours to allow management of comorbidities and reversible risk factors, alongside education, and advice to carers (who may be targets of aggression). Specialized geriatric forensic psychiatry services and care settings should be developed.
Topics: Aged; Dementia; Homicide; Humans; Psychotic Disorders; Retrospective Studies; Risk Factors
PubMed: 35306488
DOI: 10.1159/000521878 -
Schizophrenia Research Feb 2023This systematic review focuses on personality traits according to both the Five Factor Model and Cloninger Psychobiological Model in relation to treatment related... (Review)
Review
This systematic review focuses on personality traits according to both the Five Factor Model and Cloninger Psychobiological Model in relation to treatment related outcome variables across all stages of clinical psychotic illness. Search of Pubmed and Psychinfo databases led to final inclusion of 65 studies, which were ranked on quality and analyzed according to the associations between personality and outcome. Main findings are that higher levels of Harm Avoidance and Neuroticism are associated with higher symptom levels, tendency towards passive coping, greater self-stigma, lower quality of life, and Harm Avoidance to higher suicidality. Higher levels of Extraversion and higher levels of Self-Directedness are associated with more preference for active coping, more intrinsic motivation and higher self-esteem. Higher Novelty Seeking is related to more substance use and aggression, in men specifically. On outcome of trauma, care consumption and duration of untreated illness no consistent associations with personality traits were found. Combined evidence from both personality models however reveals a consistent pattern of personality traits related to clinical outcome in psychotic disorder, which is discussed in a dimensional manner.
Topics: Male; Humans; Temperament; Character; Quality of Life; Personality; Personality Disorders; Personality Inventory
PubMed: 36804473
DOI: 10.1016/j.schres.2023.01.001 -
International Journal of Geriatric... Apr 2022Although psychiatric disorders have been found to be associated with increased risk of dementia, previous findings are mixed, and the nature of these relationships... (Review)
Review
OBJECTIVES
Although psychiatric disorders have been found to be associated with increased risk of dementia, previous findings are mixed, and the nature of these relationships remains poorly understood. We examined longitudinal associations between depression, anxiety, post-traumatic stress disorders (PTSD), bipolar disorder (BPD), psychotic disorders and subsequent dementia.
METHODS
We searched three databases for longitudinal, population-based studies investigating associations between psychiatric disorders and dementia (PROSPERO registration: CRD42020209638). We conducted narrative synthesis, and random-effects meta-analyses to obtain pooled estimates. We used meta-regression and stratified analyses to examine variation by sex, age-at-onset and follow-up time.
RESULTS
Fifty-seven citations met eligibility criteria. Most studies focussed on depression (n = 33), which was associated with subsequent all-cause dementia (pooled relative risk [RR]: 1.96, 95% confidence interval [CI]: 1.59-2.43; I = 96.5%), Alzheimer's Disease (pooled RR: 1.9, 95% CI: 1.52-2.38; I = 85.5%), and Vascular Dementia (pooled RR: 2.71, 95% CI: 2.48-2.97; I = 0). Associations were stronger in studies with shorter follow-up periods and for severe and late-onset depression. Findings regarding anxiety were mixed, and we did not find evidence of an overall association (pooled RR: 1.18, 95% CI: 0.96-1.45; I = 52.2%, n = 5). Despite sparse evidence, psychotic disorders (pooled RR: 2.19, 95% CI: 1.44-3.31; I = 99%), PTSD and BPD were associated with subsequent dementia.
CONCLUSIONS
People with psychiatric disorders represent high-risk groups for dementia, highlighting the importance of ongoing symptom monitoring in these groups. Findings regarding temporality and age-at-onset indicate that depression symptoms could reflect prodromal dementia for some individuals. Further longitudinal research is required to determine whether psychiatric disorders represent causal risk factors or early markers of dementia neuropathology.
PubMed: 35460299
DOI: 10.1002/gps.5711 -
Schizophrenia Bulletin Oct 2017Ample evidence supports a neurodevelopmental origin in some cases of schizophrenia (SZ). More inconsistent information is available for bipolar disorder (BD). We herein... (Comparative Study)
Comparative Study Review
Ample evidence supports a neurodevelopmental origin in some cases of schizophrenia (SZ). More inconsistent information is available for bipolar disorder (BD). We herein review studies with a focus on premorbid (adjustment and functionality) and early developmental milestones that include both SZ and BD patients. A search was performed in the PubMed electronic database, retrieving 619 abstracts; 30 were ultimately included in this systematic review. Eight prospective cohorts, 15 retrospective studies, and 7 studies based on national registries. Psychomotor developmental deviations and general adjustment problems characterize the childhood of subjects later diagnosed with SZ or BD; they are more marked in those later diagnosed with SZ vs BD, earlier onset vs later onset, and psychotic vs nonpsychotic disorders. Cognitive impairment follows a linear risk trend for SZ and a U-shaped trend for BD. Social isolation and visuoperceptual/reading anomalies more frequently antecede SZ. Pervasive developmental disorders increase the risk for both SZ and BD, more so in cases with normal intelligence. The predictive risk of each isolated developmental marker is low, but a significant percentage of subjects with SZ and a minority of adults with BD showed signs of premorbid abnormalities in childhood. The great limitation is still the lack of studies comparing SZ and BD that include psychotic and nonpsychotic bipolar cases separately. There are many cases, even in childhood/adolescent SZ, where no premorbid anomalies are found, and immunological disorders or other etiologies should be searched for. At least in cases with clear neurodevelopmental markers, rare genetic variants should be investigated.
Topics: Bipolar Disorder; Cognitive Dysfunction; Human Development; Humans; Psychotic Disorders; Schizophrenia
PubMed: 29045744
DOI: 10.1093/schbul/sbx126 -
The Cochrane Database of Systematic... Nov 2015Schizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology. Asenapine is a recently developed atypical antipsychotic that is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Schizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology. Asenapine is a recently developed atypical antipsychotic that is approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia.
OBJECTIVES
To determine the clinical effects of asenapine for adults with schizophrenia or other schizophrenia-like disorders by comparing it with placebo.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (July 04, 2014) which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitation for inclusion of records into the register. We inspected references of all included studies for further relevant studies.
SELECTION CRITERIA
Our review includes randomised controlled trials (RCTs) comparing asenapine with placebo in adults (however defined) with schizophrenia or related disorders, including schizophreniform disorder, schizoaffective disorder and delusional disorder, again, by any means of diagnosis.
DATA COLLECTION AND ANALYSIS
We inspected citations from the searches and identified relevant abstracts, and extracted data from all included studies. For binary data we calculated risk ratio (RR) with 95% confidence intervals (CI), and for continuous data we calculated mean differences (MD). We used the GRADE approach to produce a 'Summary of findings' table which included our outcomes of interest, where possible. We used a fixed-effect model for our analyses.
MAIN RESULTS
We obtained and scrutinised 41 potentially relevant records, and from these we could include only six trials (n = 1835). Five of the six trials had high risk of attrition bias and all trials were sponsored by pharmaceutical companies. Results showed a clinically important change in global state (1 RCT, n = 336, RR 0.81, 95% CI 0.68 to 0.97, low-quality evidence) and mental state (1 RCT, n = 336, RR 0.72, 95% CI 0.59 to 0.86, very low-quality evidence) at short-term amongst people receiving asenapine. People receiving asenapine demonstrated significant reductions in negative symptoms (1 RCT, n = 336, MD -1.10, 95% CI -2.29 to 0.09, very low-quality evidence) at short-term. Individuals receiving asenapine demonstrated significantly fewer incidents of serious adverse effects (1 RCT, n = 386, RR 0.29, 95% CI 0.14 to 0.63, very low-quality evidence) at medium-term. There was no clear difference in people discontinuing the study for any reason between asenapine and placebo at short-term (5 RCTs, n = 1046, RR 0.91, 95% CI 0.80 to 1.04, very low-quality evidence). No trial reported data for extrapyramidal symptoms or costs.
AUTHORS' CONCLUSIONS
There is some, albeit preliminary, evidence that asenapine provides an improvement in positive, negative, and depressive symptoms, whilst minimising the risk of adverse effects. However due to the low-quality and limited quantity of evidence, it remains difficult to recommend the use of asenapine for people with schizophrenia. We identify a need for large-scale, longer-term, better-designed and conducted randomised controlled trials investigating the clinical effects and safety of asenapine.
Topics: Adult; Antipsychotic Agents; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 26599405
DOI: 10.1002/14651858.CD011458.pub2 -
Schizophrenia Research Nov 2023Individuals with Schizophrenia Spectrum Disorders (SSDs) have significantly higher rates of suicidal thoughts, attempts, and death by suicide in comparison to the... (Review)
Review
Individuals with Schizophrenia Spectrum Disorders (SSDs) have significantly higher rates of suicidal thoughts, attempts, and death by suicide in comparison to the general population. Sleep disturbances (reduced duration, timing and quality of sleep) are risk factors for suicidality in the general population, with research indicating the relationship is both immediate and accumulative. Sleep disturbances are also considered to be implicated in the onset and exacerbation of psychotic symptoms in SSDs. Reducing the risk of suicidality in SSDs remains an important public health priority, thus exploration of contributing risk factors is warranted. Sleep monitoring may also offer an adjunct risk monitoring method to suicidality assessments in SSDs, and a potential treatment target for psychotic symptoms. This review aimed to explore proximal and longitudinal relationships between self-reported and objectively measured sleep and suicidality in SSDs and other psychotic disorders. A comprehensive search of four databases was conducted. Eleven studies met the inclusion criteria (10 cross sectional and 1 longitudinal). Narrative synthesis indicated that self-reported sleep disturbances and sleep disorders (e.g. insomnia) were associated with increased risk of suicidal ideation and attempt. However, one study employing polysomnography did not find sleep to be associated with suicidality. Methodological limitations of the evidence base include: i) little experimental or longitudinal evidence, (ii) self-report and/or single item assessment of sleep disturbance, (iii) limited use of validated measures of suicidality, (iv) considerable research in long-term schizophrenia but sparse evidence in early psychosis. Future research should explore (i) cross-sectional and longitudinal relationships between specific aspects of suicidality and objective sleep parameters, (ii) use qualitative or mixed-methods designs to disentangle the nuances and bidirectionality in the sleep-suicide relationship, (iii) explore the psychological processes underpinning or mediating the sleep-suicide relationship in SSDs.
Topics: Humans; Suicidal Ideation; Schizophrenia; Suicide; Cross-Sectional Studies; Psychotic Disorders; Sleep; Sleep Wake Disorders; Risk Factors
PubMed: 37879227
DOI: 10.1016/j.schres.2023.10.010