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Canadian Journal of Psychiatry. Revue... May 2023Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on... (Review)
Review
Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: A Systematic Review and Recommendations of Cannabis use in Bipolar Disorder and Major Depressive Disorder.
BACKGROUND
Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on mood disorders.
OBJECTIVE
The purpose of this task force report is to examine the association between cannabis use and incidence, presentation, course and treatment of bipolar disorder and major depressive disorder, and the treatment of comorbid cannabis use disorder.
METHODS
We conducted a systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials from inception to October 2020 focusing on cannabis use and bipolar disorder or major depressive disorder, and treatment of comorbid cannabis use disorder. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of evidence and clinical considerations were integrated to generate Canadian Network for Mood and Anxiety Treatments recommendations.
RESULTS
Of 12,691 publications, 56 met the criteria: 23 on bipolar disorder, 21 on major depressive disorder, 11 on both diagnoses and 1 on treatment of comorbid cannabis use disorder and major depressive disorder. Of 2,479,640 participants, 12,502 were comparison participants, 73,891 had bipolar disorder and 408,223 major depressive disorder without cannabis use. Of those with cannabis use, 2,761 had bipolar disorder and 5,044 major depressive disorder. The lifetime prevalence of cannabis use was 52%-71% and 6%-50% in bipolar disorder and major depressive disorder, respectively. Cannabis use was associated with worsening course and symptoms of both mood disorders, with more consistent associations in bipolar disorder than major depressive disorder: increased severity of depressive, manic and psychotic symptoms in bipolar disorder and depressive symptoms in major depressive disorder. Cannabis use was associated with increased suicidality and decreased functioning in both bipolar disorder and major depressive disorder. Treatment of comorbid cannabis use disorder and major depressive disorder did not show significant results.
CONCLUSION
The data indicate that cannabis use is associated with worsened course and functioning of bipolar disorder and major depressive disorder. Future studies should include more accurate determinations of type, amount and frequency of cannabis use and select comparison groups which allow to control for underlying common factors.
Topics: Humans; Bipolar Disorder; Depressive Disorder, Major; Cannabis; Marijuana Abuse; Canada; Anxiety; Substance-Related Disorders
PubMed: 35711159
DOI: 10.1177/07067437221099769 -
Neuropsychobiology 2020Schizophrenia spectrum disorders (SSD) represent a cluster of severe mental illnesses. Diet has been identified as a modifiable risk factor and opportunity for...
INTRODUCTION
Schizophrenia spectrum disorders (SSD) represent a cluster of severe mental illnesses. Diet has been identified as a modifiable risk factor and opportunity for intervention in many physical illnesses and more recently in mental illnesses such as unipolar depression; however, no dietary guidelines exist for patients with SSD.
OBJECTIVE
This review sought to systematically scope the existing literature in order to identify nutritional interventions for the prevention or treatment of mental health symptoms in SSD as well as gaps and opportunities for further research.
METHODS
This review followed established methodological approaches for scoping reviews including an extensive a priori search strategy and duplicate screening. Because of the large volume of results, an online program (Abstrackr) was used for screening and tagging. Data were extracted based on the dietary constituents and analyzed.
RESULTS
Of 55,330 results identified by the search, 822 studies met the criteria for inclusion. Observational evidence shows a connection between the presence of psychotic disorders and poorer quality dietary patterns, higher intake of refined carbohydrates and total fat, and lower intake or levels of fibre, ω-3 and ω-6 fatty acids, vegetables, fruit, and certain vitamins and minerals (vitamin B12 and B6, folate, vitamin C, zinc, and selenium). Evidence illustrates a role of food allergy and sensitivity as well as microbiome composition and specific phytonutrients (such as L-theanine, sulforaphane, and resveratrol). Experimental studies have demonstrated benefit using healthy diet patterns and specific vitamins and minerals (vitamin B12 and B6, folate, and zinc) and amino acids (serine, lysine, glycine, and tryptophan).
DISCUSSION
Overall, these findings were consistent with many other bodies of knowledge about healthy dietary patterns. Many limitations exist related to the design of the individual studies and the ability to extrapolate the results of studies using dietary supplements to dietary interventions (food). Dietary recommendations are presented as well as recommendations for further research including more prospective observational studies and intervention studies that modify diet constituents or entire dietary patterns with statistical power to detect mental health outcomes.
Topics: Diet; Humans; Nutritional Physiological Phenomena; Psychotic Disorders; Schizophrenia
PubMed: 30359969
DOI: 10.1159/000493399 -
Frontiers in Pharmacology 2020Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a... (Review)
Review
Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a promising new agent in the treatment of psychotic and anxiety disorders. However, the neurobiological substrates underlying the potential therapeutic effects of CBD are still unclear. The aim of this systematic review is to provide a detailed and up-to-date systematic literature overview of neuroimaging studies that investigated the acute impact of CBD on human brain function. Papers published until May 2020 were included from PubMed following a comprehensive search strategy and pre-determined set of criteria for article selection. We included studies that examined the effects of CBD on brain function of healthy volunteers and individuals diagnosed with a psychiatric disorder, comprising both the effects of CBD alone as well as in direct comparison to those induced by ∆9-tetrahydrocannabinol (THC), the main psychoactive component of . One-ninety four studies were identified, of which 17 met inclusion criteria. All studies investigated the acute effects of CBD on brain function during resting state or in the context of cognitive tasks. In healthy volunteers, acute CBD enhanced fronto-striatal resting state connectivity, both compared to placebo and THC. Furthermore, CBD modulated brain activity and had opposite effects when compared to THC following task-specific patterns during various cognitive paradigms, such as emotional processing (fronto-temporal), verbal memory (fronto-striatal), response inhibition (fronto-limbic-striatal), and auditory/visual processing (temporo-occipital). In individuals at clinical high risk for psychosis and patients with established psychosis, acute CBD showed intermediate brain activity compared to placebo and healthy controls during cognitive task performance. CBD modulated resting limbic activity in subjects with anxiety and metabolite levels in patients with autism spectrum disorders. Neuroimaging studies have shown that acute CBD induces significant alterations in brain activity and connectivity patterns during resting state and performance of cognitive tasks in both healthy volunteers and patients with a psychiatric disorder. This included modulation of functional networks relevant for psychiatric disorders, possibly reflecting CBD's therapeutic effects. Future studies should consider replication of findings and enlarge the inclusion of psychiatric patients, combining longer-term CBD treatment with neuroimaging assessments.
PubMed: 33551817
DOI: 10.3389/fphar.2020.618184 -
The Cochrane Database of Systematic... Dec 2021Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an... (Review)
Review
BACKGROUND
Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an antipsychotic, another treatment (e.g. mifepristone), or combination of an antidepressant plus an antipsychotic. This is an update of a review first published in 2005 and last updated in 2015.
OBJECTIVES
1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, mifepristone monotherapy, and the combination of an antidepressant plus an antipsychotic versus placebo and/or each other. 2. To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment.
SEARCH METHODS
A search of the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR); Ovid MEDLINE (1950-); Embase (1974-); and PsycINFO (1960-) was conducted on 21 February 2020. Reference lists of all included studies and related reviews were screened and key study authors contacted.
SELECTION CRITERIA
All randomised controlled trials (RCTs) that included participants with acute major depression with psychotic features, as well as RCTs consisting of participants with acute major depression with or without psychotic features, that reported separately on the subgroup of participants with psychotic features.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias in the included studies, according to criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used intention-to-treat data. Primary outcomes were clinical response for efficacy and overall dropout rate for harm/tolerance. Secondary outcome were remission of depression, change from baseline severity score, quality of life, and dropout rate due to adverse effects. For dichotomous efficacy outcomes (i.e. response and overall dropout), risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Regarding the primary outcome of harm, only overall dropout rates were available for all studies. If the study did not report any of the response criteria as defined above, remission as defined here could be used as an alternative. For continuously distributed outcomes, it was not possible to extract data from the RCTs. MAIN RESULTS: The search identified 3947 abstracts, but only 12 RCTs with a total of 929 participants could be included in the review. Because of clinical heterogeneity, few meta-analyses were possible. The main outcome was reduction in severity (response) of depression, not of psychosis. For depression response, we found no evidence of a difference between antidepressant and placebo (RR 8.40, 95% CI 0.50 to 142.27; participants = 27, studies = 1; very low-certainty evidence) or between antipsychotic and placebo (RR 1.13, 95% CI 0.74 to 1.73; participants = 201, studies = 2; very low-certainty evidence). Furthermore, we found no evidence of a difference in overall dropouts with antidepressant (RR 1.24, 95% CI 0.34 to 4.51; participants = 27, studies = 1; very low-certainty evidence) or antipsychotic monotherapy (RR 0.79, 95% CI 0.57 to 1.08; participants = 201, studies = 2; very low-certainty evidence). No evidence suggests a difference in depression response (RR 2.09, 95% CI 0.64 to 6.82; participants = 36, studies = 1; very low-certainty evidence) or overall dropouts (RR 1.79, 95% CI 0.18 to 18.02; participants = 36, studies = 1; very low-certainty evidence) between antidepressant and antipsychotic. For depression response, low- to very low-certainty evidence suggests that the combination of an antidepressant plus an antipsychotic may be more effective than antipsychotic monotherapy (RR 1.83, 95% CI 1.40 to 2.38; participants = 447, studies = 4), more effective than antidepressant monotherapy (RR 1.42, 95% CI 1.11 to 1.80; participants = 245, studies = 5), and more effective than placebo (RR 1.86, 95% CI 1.23 to 2.82; participants = 148, studies = 2). Very low-certainty evidence suggests no difference in overall dropouts between the combination of an antidepressant plus an antipsychotic versus antipsychotic monotherapy (RR 0.79, 95% CI 0.63 to 1.01; participants = 447, studies = 4), antidepressant monotherapy (RR 0.91, 95% CI 0.55 to 1.50; participants = 245, studies = 5), or placebo alone (RR 0.75, 95% CI 0.48 to 1.18; participants = 148, studies = 2). No study measured change in depression severity from baseline, quality of life, or dropouts due to adverse events. We found no RCTs with mifepristone that fulfilled our inclusion criteria. Risk of bias is considerable: we noted differences between studies with regards to diagnosis, uncertainties around randomisation and allocation concealment, treatment interventions (pharmacological differences between various antidepressants and antipsychotics), and outcome criteria.
AUTHORS' CONCLUSIONS
Psychotic depression is heavily under-studied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone. Evidence for efficacy of mifepristone is lacking.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Major; Humans; Psychotic Disorders; Systematic Reviews as Topic
PubMed: 34875106
DOI: 10.1002/14651858.CD004044.pub5 -
Cureus Jul 2020Marijuana is one of the most abused substances in the world. Marijuana is getting legalized around the world. So, it is crucial to understand its effect on our mental... (Review)
Review
Marijuana is one of the most abused substances in the world. Marijuana is getting legalized around the world. So, it is crucial to understand its effect on our mental health. Its impact on the schizophrenia spectrum needs our special attention. Even though marijuana has been around for a long time, its exact effects are still unknown. Schizophrenia is a chronic illness affecting approximately 20 million people worldwide. Schizophrenia and cannabis seem to have a close relationship, and we want to explore this. We want to know if marijuana is causing, exacerbating, or treating schizophrenia. This systematic review explores this question. We searched online resources like PubMed, PubMed Central, Cochrane Library, and Google Scholar for systematic reviews, traditional reviews, randomized controlled trials, and meta-analysis on cannabis and schizophrenia/ psychosis. We included human studies published in peer-reviewed journals in the English language in the last five years. After reviewing 96 initial results of our search, we excluded 25 duplicates, 29 abstracts, and 18 irrelevant articles. We did a quality assessment for the remaining 24 studies using various quality assessment tools. After the quality assessment, we found 12 articles were of low quality and excluded those. We included the remaining 12 final studies in our systematic review. Out of these 12 studies, five were traditional reviews, two systematic reviews, two meta-analysis, and three observational studies. Six of the articles were on cannabis's effect on just schizophrenia or psychotic disorder. The other six included schizophrenia plus other psychiatric or neurological illnesses. Ten of the studies had data supporting the causative link between cannabis and schizophrenia. Eight records had data supporting the exacerbating effect of marijuana. Six studies had data supporting the therapeutic effect of the cannabidiol (CBD) component of cannabis. From the current data, we can conclude that the tetrahydrocannabinol (THC) component of cannabis can be the main culprit causing psychosis and schizophrenia in the at-risk population. THC can also be the one exacerbating symptoms and causing an adverse prognosis in already diagnosed patients. Even though CBD shows therapeutic effects and THC opposing effects, the data is minimal and low safety and efficacy warrants more research. The relation between cannabis and schizophrenia needs further investigation. We need more case-control studies and clinical trials with a larger population to get conclusive data.
PubMed: 32839678
DOI: 10.7759/cureus.9309 -
PloS One 2021Antipsychotic agents are the basis for the pharmacological management of acute and chronic schizophrenia, bipolar disorders, mood disorders with psychotic feature, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antipsychotic agents are the basis for the pharmacological management of acute and chronic schizophrenia, bipolar disorders, mood disorders with psychotic feature, and other psychotic disorders. Antipsychotic medication use is frequently associated with unfavorable adverse effects such as extrapyramidal side effects (EPSEs). Hence, this systematic review and meta-analysis was aimed to determine the magnitude of antipsychotic-induced EPSEs.
METHOD
A literature search was conducted using legitimate databases, indexing services, and directories including PubMed/MEDLINE (Ovid®), EMBASE (Ovid®), google scholar and WorldCat to retrieve studies. Following screening and eligibility, the relevant data were extracted from the included studies using an Excel sheet and exported to STATA 15.0 software for analyses. The Random effects pooling model was used to analyze outcome measures at a 95% confidence interval. Besides, publication bias analysis was conducted. The protocol has been registered on PROSPERO with ID: CRD42020175168.
RESULT
In total, 15 original articles were included for the systematic review and meta-analysis. The pooled prevalence of antipsychotic-induced EPSEs among patient taking antipsychotic medications was 37% (95% CI: 18-55%, before sensitivity) and 31% (95% CI: 19-44%, after sensitivity). The prevalence of antipsychotic-induced parkinsonism, akathisia, and tardive dyskinesia was 20% (95% CI: 11-28%), 11% (95% CI: 6-17%), and 7% (95% CI: 4-9%), respectively. To confirm a small-study effect, Egger's regression test accompanied by funnel plot asymmetry demonstrated that there was a sort of publication bias in studies reporting akathisia and tardive dyskinesia.
CONCLUSION
The prevalence of antipsychotic-induced EPSEs was considerably high. One in five and more than one in ten patients experienced parkinsonism and akathisia, respectively. Appropriate prevention and early management of these effects can enhance the net benefits of antipsychotics.
Topics: Antipsychotic Agents; Geography; Humans; Movement Disorders; Observational Studies as Topic; Outcome Assessment, Health Care; Publication Bias; Tardive Dyskinesia
PubMed: 34506552
DOI: 10.1371/journal.pone.0257129 -
Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia.The Cochrane Database of Systematic... Dec 2021Typical and atypical antipsychotics are widely used to treat agitation and psychosis in dementia. However, whether or not they are beneficial is uncertain. Some trials... (Review)
Review
BACKGROUND
Typical and atypical antipsychotics are widely used to treat agitation and psychosis in dementia. However, whether or not they are beneficial is uncertain. Some trials have yielded negative results and effectiveness may be outweighed by harms.
OBJECTIVES
To assess the efficacy and safety of antipsychotics for the treatment of agitation and psychosis in people with Alzheimer's disease and vascular dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid Sp), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register, and the International Clinical Trials Registry Portal on 7 January 2021. Two review authors independently screened the title and abstract of the hits, and two review authors assessed the full text of studies that got through this screening.
SELECTION CRITERIA
We included randomised, placebo-controlled, parallel-arm trials comparing the effects of antipsychotics and placebo for the treatment of agitation or psychosis in people with dementia due to Alzheimer's disease or vascular dementia, or both, irrespective of age, severity of cognitive impairment, and setting. (The majority of) participants had to have clinically significant agitation (including aggression) or psychosis or both at baseline. We excluded studies about antipsychotics that are no longer available in the USA or EU, or that are used for emergency short-term sedation. We also excluded head-to-head trials and antipsychotic withdrawal trials.
DATA COLLECTION AND ANALYSIS
The primary outcomes were (1) reduction in agitation or psychosis in participants with agitation or psychosis, respectively at baseline, and (2) the number of participants with adverse events: somnolence, extrapyramidal symptoms, any adverse event, any serious adverse event (SAE), and death. Two review authors independently extracted the necessary data and assessed risk of bias with the Cochrane risk of bias tool. We calculated the pooled effect on agitation and psychosis for typical and atypical antipsychotics separately, and the pooled risk of adverse effects independent of the target symptom (agitation or psychosis). We used RevMan Web for the analyses.
MAIN RESULTS
The search yielded 8233 separate hits. After assessing the full-text of 35 studies, we included 24 trials that met the eligibility criteria. Six trials tested a typical antipsychotic, four for agitation and two for psychosis. Twenty trials tested an atypical antipsychotic, eight for agitation and 12 for psychosis. Two trials tested both drug types. Seventeen of 26 comparisons were performed in patients with Alzheimer's disease specifically. The other nine comparisons also included patients with vascular dementia or mixed dementia. Together, the studies included 6090 participants (12 to 652 per study). The trials were performed in institutionalised, hospitalised and community-dwelling patients, or a combination of those. For typical antipsychotics (e.g. haloperidol, thiothixene), we are uncertain whether these drugs improve agitation compared with placebo (standardised mean difference (SMD) -0.36, 95% confidence interval (CI) -0.57 to -0.15, 4 studies, n = 361); very low-certainty evidence, but typical antipsychotics may improve psychosis slightly (SMD -0.29, 95% CI -0.55 to -0.03, 2studies, n= 240; low-certainty evidence) compared with placebo. These drugs probably increase the risk of somnolence (risk ratio (RR) 2.62, 95% CI 1.51 to 4.56, 3 studies, n = 466; moderate-certainty evidence) and increase extrapyramidal symptoms (RR 2.26, 95% CI 1.58 to 3.23, 3 studies, n = 467; high-certainty) evidence. There was no evidence regarding the risk of any adverse event. The risks of SAEs (RR 1.32, 95% CI 0.65 to 2.66, 1 study, n = 193) and death (RR 1.46, 95% CI 0.54 to 4.00, 6 studies, n = 578) may be increased slightly, but these estimates were very imprecise, and the certainty was low. The effect estimates for haloperidol from five trials were in line with those of the drug class. Atypical antipsychotics (e.g. risperidone, olanzapine, aripiprazole, quetiapine) probably reduce agitation slightly (SMD -0.21, 95% CI -0.30 to -0.12, 7 studies, n = 1971; moderate-certainty evidence), but probably have a negligible effect on psychosis (SMD -0.11, 95% CI -0.18 to -0.03, 12 studies, n = 3364; moderate-certainty evidence). These drugs increase the risk of somnolence (RR 1.93, 95% CI 1.57 to 2.39, 13 studies, n - 3878; high-certainty evidence) and are probably also associated with slightly increased risk of extrapyramidal symptoms (RR 1.39, 95% CI 1.14 to 1.68, 15 studies, n = 4180; moderate-certainty evidence), serious adverse events (RR 1.32, 95% CI 1.09 to 1.61, 15 studies, n= 4316; moderate-certainty evidence) and death (RR 1.36, 95% CI 0.90 to 2.05, 17 studies, n= 5032; moderate-certainty evidence), although the latter estimate was imprecise. The drugs probably have a negligible effect on the risk of any adverse event (RR 1.05, 95% CI 1.02 to 1.09, 11 studies, n = 2785; moderate-certainty evidence). The findings from seven trials for risperidone were in line with those for the drug class.
AUTHORS' CONCLUSIONS
There is some evidence that typical antipsychotics might decrease agitation and psychosis slightly in patients with dementia. Atypical antipsychotics reduce agitation in dementia slightly, but their effect on psychosis in dementia is negligible. The apparent effectiveness of the drugs seen in daily practice may be explained by a favourable natural course of the symptoms, as observed in the placebo groups. Both drug classes increase the risk of somnolence and other adverse events. If antipsychotics are considered for sedation in patients with severe and dangerous symptoms, this should be discussed openly with the patient and legal representative.
Topics: Alzheimer Disease; Antipsychotic Agents; Dementia, Vascular; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic; Risperidone
PubMed: 34918337
DOI: 10.1002/14651858.CD013304.pub2 -
The Lancet. Psychiatry Apr 2020Approximately 188 million people use cannabis yearly worldwide, and it has recently been legalised in 11 US states, Canada, and Uruguay for recreational use. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 188 million people use cannabis yearly worldwide, and it has recently been legalised in 11 US states, Canada, and Uruguay for recreational use. The potential for increased cannabis use highlights the need to better understand its risks, including the acute induction of psychotic and other psychiatric symptoms. We aimed to investigate the effect of the cannabis constituent Δ-tetrahydrocannabinol (THC) alone and in combination with cannabidiol (CBD) compared with placebo on psychiatric symptoms in healthy people.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published in English between database inception and May 21, 2019, with a within-person, crossover design. Inclusion criteria were studies reporting symptoms using psychiatric scales (the Brief Psychiatric Rating Scale [BPRS] and the Positive and Negative Syndrome Scale [PANSS]) following the acute administration of intravenous, oral, or nasal THC, CBD, and placebo in healthy participants, and presenting data that allowed calculation of standardised mean change (SMC) scores for positive (including delusions and hallucinations), negative (such as blunted affect and amotivation), and general (including depression and anxiety) symptoms. We did a random-effects meta-analysis to assess the main outcomes of the effect sizes for total, positive, and negative PANSS and BPRS scores measured in healthy participants following THC administration versus placebo. Because the number of studies to do a meta-analysis on CBD's moderating effects was insufficient, this outcome was only systematically reviewed. This study is registered with PROSPERO, CRD42019136674.
FINDINGS
15 eligible studies involving the acute administration of THC and four studies on CBD plus THC administration were identified. Compared with placebo, THC significantly increased total symptom severity with a large effect size (assessed in nine studies, with ten independent samples, involving 196 participants: SMC 1·10 [95% CI 0·92-1·28], p<0·0001); positive symptom severity (assessed in 14 studies, with 15 independent samples, involving 324 participants: SMC 0·91 [95% CI 0·68-1·14], p<0·0001); and negative symptom severity with a large effect size (assessed in 12 studies, with 13 independent samples, involving 267 participants: SMC 0·78 [95% CI 0·59-0·97], p<0·0001). In the systematic review, of the four studies evaluating CBD's effects on THC-induced symptoms, only one identified a significant reduction in symptoms.
INTERPRETATION
A single THC administration induces psychotic, negative, and other psychiatric symptoms with large effect sizes. There is no consistent evidence that CBD induces symptoms or moderates the effects of THC. These findings highlight the potential risks associated with the use of cannabis and other cannabinoids that contain THC for recreational or therapeutic purposes.
FUNDING
UK Medical Research Council, Maudsley Charity, Brain and Behavior Research Foundation, Wellcome Trust, and the UK National Institute for Health Research.
Topics: Administration, Inhalation; Cannabidiol; Dronabinol; Drug Combinations; Drug Interactions; Hallucinogens; Humans; Marijuana Smoking; Psychoses, Substance-Induced
PubMed: 32197092
DOI: 10.1016/S2215-0366(20)30074-2 -
JAMA Psychiatry Feb 2022Violence perpetration outcomes in individuals with schizophrenia spectrum disorders contribute to morbidity and mortality at a population level, disrupt care, and lead... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Violence perpetration outcomes in individuals with schizophrenia spectrum disorders contribute to morbidity and mortality at a population level, disrupt care, and lead to stigma.
OBJECTIVE
To conduct a systematic review and meta-analysis of the risk of perpetrating interpersonal violence in individuals with schizophrenia spectrum disorders compared with general population control individuals.
DATA SOURCES
Multiple databases were searched for studies in any language from January 1970 to March 2021 using the terms violen* or homicid* and psychosis or psychoses or psychotic or schizophren* or schizoaffective or delusional and terms for mental disorders. Bibliographies of included articles were hand searched.
STUDY SELECTION
The study included case-control and cohort studies that allowed risks of interpersonal violence perpetration and/or violent criminality in individuals with schizophrenia spectrum disorders to be compared with a general population group without these disorders.
DATA EXTRACTION AND SYNTHESIS
The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and the Meta-analyses of Observational Studies in Epidemiology (MOOSE) proposal. Two reviewers extracted data. Quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
The main outcome was violence to others obtained either through official records, self-report and/or collateral-report, or medical file review and included any physical assault, robbery, sexual offenses, illegal threats or intimidation, and arson.
RESULTS
The meta-analysis included 24 studies of violence perpetration outcomes in 15 countries over 4 decades (N = 51 309 individuals with schizophrenia spectrum disorders; reported mean age of 21 to 54 years at follow-up; of those studies that reported outcomes separately by sex, there were 19 976 male individuals and 14 275 female individuals). There was an increase in risk of violence perpetration in men with schizophrenia and other psychoses (pooled odds ratio [OR], 4.5; 95% CI, 3.6-5.6) with substantial heterogeneity (I2 = 85%; 95% CI, 77-91). The risk was also elevated in women (pooled OR, 10.2; 95% CI, 7.1-14.6), with substantial heterogeneity (I2 = 66%; 95% CI, 31-83). Odds of perpetrating sexual offenses (OR, 5.1; 95% CI, 3.8-6.8) and homicide (OR, 17.7; 95% CI, 13.9-22.6) were also investigated. Three studies found increased relative risks of arson but data were not pooled for this analysis owing to heterogeneity of outcomes. Absolute risks of violence perpetration in register-based studies were less than 1 in 20 in women with schizophrenia spectrum disorders and less than 1 in 4 in men over a 35-year period.
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis found that the risk of perpetrating violent outcomes was increased in individuals with schizophrenia spectrum disorders compared with community control individuals, which has been confirmed in new population-based longitudinal studies and sibling comparison designs.
Topics: Adolescent; Adult; Databases, Factual; Humans; Psychotic Disorders; Schizophrenia; Violence
PubMed: 34935869
DOI: 10.1001/jamapsychiatry.2021.3721 -
Schizophrenia Research Dec 2022The aim was to examine the general outcome of schizophrenia after 20 years or more. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim was to examine the general outcome of schizophrenia after 20 years or more.
METHODS
Using the PRISMA guidelines, we conducted a systematic review and meta-analysis with meta-regression on long-term follow-up studies of schizophrenia up until April 21, 2021. We included prospective studies with at least 20 years of follow-up on patients with a diagnosis of schizophrenia, and the studies had to include face-to-face clinical evaluation. We examined outcome in three nested groups: 'recovery', 'good or better' (including also 'recovery'), and 'moderate or better' (including also 'recovery' and 'good or better'). We used random-effects meta-analysis and meta-regression to examine mean estimates and possible moderators.
RESULTS
We identified 1089 records, which were screened by two independent researchers. 14 prospective studies (1991 patients) published between 1978 and 2020 were found eligible. The studies used a range of different scales and definitions for outcome, and some used the same definitions for different outcomes. To compare outcome across studies, we designed and applied a unified template for outcome definitions and cutoffs, based on earlier studies' recommendations. Our meta-analysis found that 24.2 % had 'recovered' (n = 246, CI: 20.3-28.0 %), 35.5 % had a 'good or better' outcome (n = 766, CI: 26.0-45.0%), and 59.7% had 'moderate or better' outcome (n = 1139, CI: 49.3-70.1 %).
CONCLUSIONS
The results contribute to debunk the myth that schizophrenia inevitably has a deteriorating course. Recovery is certainly possible. Schizophrenia remains, however, a severe and complex mental disorder, exhibiting a limited change in prognosis despite >100 years of research and efforts to improve treatment.
Topics: Humans; Schizophrenia; Follow-Up Studies; Prospective Studies; Psychotic Disorders; Prognosis
PubMed: 36417817
DOI: 10.1016/j.schres.2022.11.010