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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 -
BMC Psychiatry Oct 2016Most antipsychotics are associated with weight gain and other metabolic complications. Several randomized trials have shown metformin to be effective, but this still... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most antipsychotics are associated with weight gain and other metabolic complications. Several randomized trials have shown metformin to be effective, but this still hasn't been included in clinical guidelines on managing antipsychotic induced weight gain.
METHODS
All double blind placebo controlled trials assessing the efficacy of metformin in the treatment of antipsychotic induced weight gain were included. Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE were searched for the period January 2000-December 2015. Meta-analysis was carried out using the random effects model.
RESULTS
Meta analysis of 12 published studies with a total of 743 patients found that in patients treated with antipsychotics, metformin treatment resulted in significantly better anthropometric and metabolic parameters than placebo. The mean change in weight was -3.27 kg (95 % CI -4.66 to -1.89) (Z = 4.64, p < 0.001). Metformin compared to placebo resulted in significant reduction in BMI [-1.13 kg/m (95 % CI -1.61 to -0.66)] and insulin resistance index [-1.49 (95 % CI -2.40 to -0.59)] but not fasting blood sugar [-2.48 mg/dl (95 % CI -5.54 to 0.57].
CONCLUSION
This meta-analysis confirms that metformin is effective in treating antipsychotic induced weight gain in patients with schizophrenia or schizoaffective disorder.
Topics: Antipsychotic Agents; Double-Blind Method; Humans; Metformin; Psychotic Disorders; Schizophrenia; Weight Gain
PubMed: 27716110
DOI: 10.1186/s12888-016-1049-5 -
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 -
Schizophrenia Bulletin Jan 2017Hallucinations constitute one of the 5 symptom domains of psychotic disorders in DSM-5, suggesting diagnostic significance for that group of disorders. Although specific... (Review)
Review
Hallucinations constitute one of the 5 symptom domains of psychotic disorders in DSM-5, suggesting diagnostic significance for that group of disorders. Although specific featural properties of hallucinations (negative voices, talking in the third person, and location in external space) are no longer highlighted in DSM, there is likely a residual assumption that hallucinations in schizophrenia can be identified based on these candidate features. We investigated whether certain featural properties of hallucinations are specifically indicative of schizophrenia by conducting a systematic review of studies showing direct comparisons of the featural and clinical characteristics of (auditory and visual) hallucinations among 2 or more population groups (one of which included schizophrenia). A total of 43 articles were reviewed, which included hallucinations in 4 major groups (nonclinical groups, drug- and alcohol-related conditions, medical and neurological conditions, and psychiatric disorders). The results showed that no single hallucination feature or characteristic uniquely indicated a diagnosis of schizophrenia, with the sole exception of an age of onset in late adolescence. Among the 21 features of hallucinations in schizophrenia considered here, 95% were shared with other psychiatric disorders, 85% with medical/neurological conditions, 66% with drugs and alcohol conditions, and 52% with the nonclinical groups. Additional differences rendered the nonclinical groups somewhat distinctive from clinical disorders. Overall, when considering hallucinations, it is inadvisable to give weight to the presence of any featural properties alone in making a schizophrenia diagnosis. It is more important to focus instead on the co-occurrence of other symptoms and the value of hallucinations as an indicator of vulnerability.
Topics: Hallucinations; Humans; Schizophrenia
PubMed: 27872259
DOI: 10.1093/schbul/sbw132 -
BioMed Research International 2015Behavioral and psychological symptoms of dementia (BPSD) are defined as a group of symptoms of disturbed perceptive thought content, mood, or behavior that include... (Review)
Review
INTRODUCTION
Behavioral and psychological symptoms of dementia (BPSD) are defined as a group of symptoms of disturbed perceptive thought content, mood, or behavior that include agitation, depression, apathy, repetitive questioning, psychosis, aggression, sleep problems, and wandering. Care of patients with BPSD involves pharmacological and nonpharmacological interventions. We reviewed studies of nonpharmacological interventions published in the last 10 years.
METHODS
We performed a systematic review in Medline and Embase databases, in the last 10 years, until June 2015. Key words used were (1) non-pharmacological interventions, (2) behavioral symptoms, (3) psychological symptoms, and (4) dementia.
RESULTS
We included 20 studies published in this period. Among these studies, program activities were more frequent (five studies) and the symptoms more responsive to the interventions were agitation.
DISCUSSION
Studies are heterogeneous in many aspects, including size sample, intervention, and instruments of measures.
CONCLUSION
Nonpharmacological interventions are able to provide positive results in reducing symptoms of BPSD. Most studies have shown that these interventions have important and significant efficacy.
Topics: Aggression; Dementia; Depression; Humans; Musculoskeletal Manipulations; Psychomotor Agitation; Psychotic Disorders
PubMed: 26693477
DOI: 10.1155/2015/218980 -
PloS One 2022Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of... (Review)
Review
AIM
Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of schizophrenia. This study aims to provide a comprehensive review on the efficacy of first-generation and second-generation LAI antipsychotics in recent-onset, first-episode, and early psychosis patients.
METHODS
MEDLINE, EMBASE, PsycINFO, and Web of Science Core databases were used to search for studies that used LAIs in early psychosis patients. Studies published up to 06 Jun 2019 were included with no language restrictions applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years.
RESULTS
33 studies were included: 8 RCTs, 4 post-hoc analyses, 2 case reports, and 19 naturalistic studies. The majority of studies evaluated risperidone LAIs (N = 14) and paliperidone palmitate (N = 10), while the remainder investigated fluphenazine decanoate (N = 3), flupentixol decanoate (N = 2), and aripiprazole (N = 1). Two studies did not specify the LAI formulation used, and one cohort study compared the efficacy of multiple different LAI formulations.
CONCLUSIONS
While the majority of data is based on naturalistic studies investigating risperidone LAIs or paliperidone palmitate, LAIs may be an effective treatment for early psychosis patients in terms of adherence, relapse reduction, and symptom improvements. There is still a need to conduct more high quality RCTs that investigate the efficacy of different LAI formulations in early psychosis patients.
Topics: Antipsychotic Agents; Cohort Studies; Delayed-Action Preparations; Humans; Paliperidone Palmitate; Psychotic Disorders; Risperidone
PubMed: 35486616
DOI: 10.1371/journal.pone.0267808 -
European Neuropsychopharmacology : the... Nov 2023Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a... (Meta-Analysis)
Meta-Analysis Review
Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a dose-response meta-analysis to find the optimal dosage of psilocybin to reduce depression scores. Following our protocol (CRD 42022220190) multiple electronic databases were searched from their inception until February 2023, to identify double-blind randomized placebo-controlled (RCTs) fixed-dose trials evaluating the use of psilocybin for adult patients with primary or secondary depression. A one-stage dose-response meta-analysis with restricted cubic splines was used. Cochrane risk of bias was used to assess risk of bias. Our analysis included seven studies with a total of 489 participants. Among these, four studies focused on primary depression (N = 366), including one study with patients suffering from treatment-resistant depression. The remaining three studies examined secondary depression (N = 123). The determined 95% effective doses per day (ED95) were 8.92, 24.68, and 36.08 mg/70 kg for patients with secondary depression, primary depression, and both subgroups, respectively. We observed significant dose-response associations for all curves, each plateauing at different levels, except for the bell-shaped curve observed in the case of secondary depression. Additionally, we found significant dose-response associations for various side effects, including physical discomfort, blood pressure increase, nausea/vomiting, headache/migraine, and the risk of prolonged psychosis. In conclusion, we discovered specific ED95 values for different populations, indicating higher ED95 values for treatment-resistant depression, primary depression, and secondary depression groups. Further RCTs are necessary for each population to determine the optimal dosage, allowing for maximum efficacy while minimizing side effects.
Topics: Adult; Humans; Depression; Psilocybin; Antidepressive Agents; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 37557019
DOI: 10.1016/j.euroneuro.2023.07.011 -
Environmental Health Perspectives Dec 2019Particulate air pollution's physical health effects are well known, but associations between particulate matter (PM) exposure and mental illness have not yet been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Particulate air pollution's physical health effects are well known, but associations between particulate matter (PM) exposure and mental illness have not yet been established. However, there is increasing interest in emerging evidence supporting a possible etiological link.
OBJECTIVES
This systematic review aims to provide a comprehensive overview and synthesis of the epidemiological literature to date by investigating quantitative associations between PM and multiple adverse mental health outcomes (depression, anxiety, bipolar disorder, psychosis, or suicide).
METHODS
We undertook a systematic review and meta-analysis. We searched Medline, PsycINFO, and EMBASE from January 1974 to September 2017 for English-language human observational studies reporting quantitative associations between exposure to PM in aerodynamic diameter (ultrafine particles) and PM and in aerodynamic diameter ( and , respectively) and the above psychiatric outcomes. We extracted data, appraised study quality using a published quality assessment tool, summarized methodological approaches, and conducted meta-analyses where appropriate.
RESULTS
Of 1,826 citations identified, 22 met our overall inclusion criteria, and we included 9 in our primary meta-analyses. In our meta-analysis of associations between long-term () exposure and depression ( studies), the pooled odds ratio was 1.102 per increase (95% CI: 1.023, 1.189; ). Two of the included studies investigating associations between long-term exposure and anxiety also reported statistically significant positive associations, and we found a statistically significant association between short-term exposure and suicide in meta-analysis at a 0-2 d cumulative exposure lag.
DISCUSSION
Our findings support the hypothesis of an association between long-term exposure and depression, as well as supporting hypotheses of possible associations between long-term exposure and anxiety and between short-term exposure and suicide. The limited literature and methodological challenges in this field, including heterogeneous outcome definitions, exposure assessment, and residual confounding, suggest further high-quality studies are warranted to investigate potentially causal associations between air pollution and poor mental health. https://doi.org/10.1289/EHP4595.
Topics: Air Pollutants; Air Pollution; Bipolar Disorder; Depression; Disease Susceptibility; Environmental Exposure; Humans; Psychotic Disorders; Risk Factors; Suicide
PubMed: 31850801
DOI: 10.1289/EHP4595 -
World Psychiatry : Official Journal of... Oct 2015Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta-analysis was to assess...
Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis.
Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta-analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%-34.4%; N = 198; n = 52,678). Relative risk meta-analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta-analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = -3.6, p = 0.0003, r(2) = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic-naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35-1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.
PubMed: 26407790
DOI: 10.1002/wps.20252