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Purpose: The evidence of the neuropsychiatric effects associated with fluoroquinolones is mainly supported by case reports. Population-based evidence remains largely limited. We aimed to investigate the association between the use of fluoroquinolones and hospitalization or Accident & Emergency department visits for acute neuropsychiatric events using a self-controlled case series (SCCS) and active comparator to reduce confounding., Methods: We conducted a SCCS with a recently described active comparator design using all public outpatient clinics, hospitalization, and Accident and Emergency department records from the Clinical Data Analysis and Reporting System, Hong Kong from 2001 to 2013. Among 166 325 people with an oral fluoroquinolone prescription, 4287 people who had an incident neuropsychiatric event were included. We then estimated the incidence rate ratio (IRR) of acute neuropsychiatric events during periods before and after fluoroquinolone prescription, versus baseline. We repeated the analysis for amoxicillin/clavulanic acid users as an active comparator. We then estimated the comparator-adjusted estimates by dividing the IRR for fluoroquinolone by the IRR for amoxicillin/clavulanic acid. The primary outcome was neuropsychiatric events. Secondary outcomes were psychotic events and cognitive impairment., Results: An increased risk of neuropsychiatric events was observed in the current use of fluoroquinolone [IRR: 2.11 (95% confidence interval (CI): 1.58-2.83)] and 1-7 days after the end of fluoroquinolone prescription [IRR: 1.90 (95% CI: 1.30-2.75)] versus baseline. No increased risk was observed in other risk periods versus baseline. Similar patterns were observed in the current use of amoxicillin/clavulanic acid [IRR: 1.92 (95% CI: 1.19-3.11)] and 1-7 days after the end of fluoroquinolone prescription [IRR: 1.81 (95% CI: 1.11-2.97)] versus baseline. Similar results were found for secondary outcomes. Using the active comparator design, comparator-adjusted estimates were 1.10 (95% CI: 0.63-1.93) in current use of fluoroquinolones and 1.05 (95% CI: 0.57-1.95) in 1-7 days postexposure to fluoroquinolones versus baseline., Conclusions: Although our study showed a higher incidence of neuropsychiatric events in the current use of fluoroquinolones and 7 days after the end of fluoroquinolones prescriptions compared with baseline, a similar temporal pattern was also found for amoxicillin/clavulanic acid users. Using amoxicillin/clavulanic acid as the active comparator, we found no difference in the risk of neuropsychiatric events associated with fluoroquinolone compared with baseline. Therefore, the risk of neuropsychiatric events may not need to influence the decision to prescribe either fluoroquinolones or amoxicillin/clavulanic acid based on the evidence in this study., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Objective: Amphetamine prescribing has increased in the United States in recent years. Previous research identified an increased risk of incident psychosis with prescription amphetamines. The purpose of this study was to examine the impact of dose levels of prescription amphetamines on the risk of this rare but serious adverse outcome., Methods: A case-control study using electronic health records was conducted to compare the odds of incident psychosis or mania with past-month exposure to prescription amphetamines. Case subjects were patients ages 16-35 hospitalized at McLean Hospital for incident psychosis or mania between 2005 and 2019. Control subjects were patients with an initial psychiatric hospitalization for other reasons, most commonly depression and/or anxiety. Amphetamine doses were converted to dextroamphetamine equivalents and divided into terciles. Secondary analyses evaluated the odds of psychosis or mania with methylphenidate use., Results: Among 1,374 case subjects and 2,748 control subjects, the odds of psychosis and mania were increased for individuals with past-month prescription amphetamine use compared with no use (adjusted odds ratio=2.68, 95% CI=1.90-3.77). A dose-response relationship was observed; high doses of amphetamines (>30 mg dextroamphetamine equivalents) were associated with 5.28-fold increased odds of psychosis or mania. Past-month methylphenidate use was not associated with increased odds of psychosis or mania compared with no use (adjusted odds ratio=0.91, 95% CI=0.54-1.55)., Conclusions: Although use of hospitalized control subjects excludes individuals with less severe disease, leading to selection bias, the study results suggest that caution should be exercised when prescribing high doses of amphetamines, with regular screening for symptoms of psychosis or mania., Competing Interests: Dr. Moran is employed by Sage Therapeutics. Dr. Perlis has served as a scientific adviser for Alkermes, Belle Artificial Intelligence, Burrage Capital, Circular Genomics, Genomind, Mila Health, Psy Therapeutics, Swan AI Studios, and Vault Health. Dr. Ongur has received honoraria from Boehringer Ingelheim, Guggenheim LLC, and Neumora for scientific presentations. The other authors report no financial relationships with commercial interests.

Background: Current treatment of cannabis-induced psychosis (CIP) focus on the presenting symptoms of individual patient. Therefore, the objective of this study was to investigate the efficacy of pharmacological treatment for CIP in a retrospective manner., Methods: A retrospective chart review study was conducted at the Princess Mother National Institute on Drug Abuse Treatment (PMNIDAT), Thailand. Patients aged more than 12 years who met the International Classification of Disease-10 (ICD-10) criteria of CIP, had recorded of cannabis use in medical chart, and had positive urine test of cannabis on the first day of admission from October 2013 to September 2019 were enrolled. The primary outcome was the efficacy of pharmacological treatment of CIP. Brief Psychotic Rating Scale (BPRS) on the first day and weekly after receiving treatment were used to assess the primary outcome., Results: Four hundred and three medical charts with diagnosis of CIP were enrolled into the study and only 317 charts were analyzed. Most of them were male with an average aged of 21.0 (19.0-24.0) years old. All of them used smoked cannabis from dried leaves and flowers of cannabis plant. The presented symptoms on admission were psychosis, mood symptoms, sleep problems, weight loss, and cognitive problems (100%, 64%, 61%, 11%, and 7%, respectively). Baseline BPRS score of the first day of admission was 55.2 ± 9.6. Majority of patients received antipsychotic (98.7%) followed by the combination of antipsychotics with benzodiazepines (34.5.%), antipsychotics with antidepressants (14.4%) and antipsychotics treatment with antidepressants and benzodiazepines (25.9%). Only few patients received antipsychotic monotherapy (17.9%). Risperidone was the most frequently prescribed antipsychotics (83.6%). Mean equivalence dose of risperidone was 8.0 ± 5.9 mg/day. The average hospital length of stay was 28 days (range 22-31). BPRS at 22 days significantly improved compared to the first day of admission (p < 0.001). Schizophrenia was diagnosed in 7% at 1.3 years of follow up., Conclusion: Antipsychotics was still a key psychotropic drug for treatment of CIP. The symptoms were decreased rapidly and sustained among the treatment period. However, antidepressants and benzodiazepines were commonly used for treatment of other symptoms beyond psychosis., Trial Registration: ClinicalTrials.gov ID: NCT04945031 (Registration Date: 30 June, 2021)., (© 2024. The Author(s).)

Background and Aims: High-potency cannabis has been associated with increased risk of psychosis, but a lack of prospective data hinders understanding of causality in this relationship. This study aimed to combine prospective report of cannabis use with retrospective report of potency to infer the potency of cannabis used in adolescence and explore whether use of cannabis, and the use of high-potency cannabis, in adolescence is associated with incident psychotic experiences., Design: Population-based birth cohort study., Setting: United Kingdom., Participants: n = 5570 participants who reported on any cannabis use (yes/no) age 16 and 18 years, and n = 1560 participants from this group who also retrospectively reported on cannabis potency., Measurements: In questionnaires at ages 16 and 18, individuals self-reported lifetime cannabis use, and at age 24, participants reported the type of cannabis they most commonly used in the whole time since first using cannabis. Psychotic experiences were assessed at age 24 years using the semi-structured Psychosis-Like Symptom Interview, with incident defined as new-onset occurring between ages 19 and 24 years., Findings: Use of high-potency cannabis at age 16 or 18 was associated with twice the likelihood of experiencing incident psychotic experiences from age 19-24 (Odds Ratio 2.15, 95% Confidence Intervals 1.13-4.06). There was less evidence for an effect of any cannabis use on incident psychotic experiences (Odds Ratio 1.45, 95% Confidence Intervals 0.94-2.12)., Conclusions: Use of high-potency cannabis appears to be associated with increased likelihood of psychotic experiences., (© 2024 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Rationale: Synthetic cathinones (SC), commonly referred to as "bath salts", are stimulants resembling the natural alkaloid cathinone found in the khat plant. These substances have the potential to induce serious health risks such as hallucinations, delusions, paranoia and agitation which can lead to substance-induced psychotic disorders. Despite growing concerns, there is a limited understanding of the association between SC consumption and the devolvement of such psychopathologies., Methods: We conducted a systematic review to investigate the frequency of substance-induced psychotic disorder (SIPD) and associated conditions in humans following synthetic cathinone consumption. We qualitatively and quantitatively analyzed SC exposure cases., Results: A total of 32 studies were included, with a diverse range of demographics, synthetic cathinone types, and consumption patterns. The proportion of individuals developing psychotic symptoms was reported at 0.380 (Random-effects model, 95% CI 0.289 - 0.475). Additionally, the significant heterogeneity in diagnostic approaches limited our ability to provide a precise estimate of prevalence., Conclusions: Synthetic cathinone consumption is associated with the risk of developing psychotic symptoms as indicated by the prevalence of hallucinations and/or delusions. Due to the lack of information on classifying factors, particularly duration of symptoms, we are unable to conclude synthetic cathinone-induced psychosis. Further research is warranted to elucidate the underlying mechanism linking synthetic cathinone consumption and psychosis. This review underscores the urgency of addressing the growing health risks posed by synthetic cathinone use. Additionally, it highlights the necessity of proper quantification of psychotic symptoms through scales and reporting of classification criteria to accurately diagnose SIPD., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Substance-induced psychosis (SIP) is a serious condition and may predispose for schizophrenia. We know too little about SIP incidence over time and across countries, including substance-specific SIPs. We estimated annual incidence rate of SIP in Denmark, Norway, and Sweden according to substance, age, gender, and socioeconomic background., Methods: Data were drawn from registries covering the whole adult population in the countries. Annual incidence rate per 100 000 persons of SIPs was estimated for Denmark and Sweden from 2000 to 2016 and for Norway from 2010 to 2015., Results: The annual incidence rate of any SIP fluctuated between 9.3 and 14.1. The most commonly occurring SIPs were those induced by alcohol, cannabis, amphetamines, and multiple substances. There was a steady decrease in the incidence rate of alcohol-induced psychosis from the first to the last year of the observation period in Denmark (from 4.9 to 1.5) and Sweden (from 4.5 to 2.2). The incidence rate of cannabis-induced psychosis increased in all countries, from 2.6 to 5.6 in Denmark, from 0.8 to 2.7 in Sweden, and from 1.8 to 3.0 in Norway. Median age of any SIP decreased in Denmark (from 36 to 29 years) and Sweden (from 41 to 31 years). Incidence rates were higher in men and in individuals on disability pension, and increased more among those with high parental education., Conclusions: We found similar and stable incidence rates of any SIP in all Scandinavian countries through the observation period. The incidence of alcohol-induced psychosis decreased. The incidence of cannabis-induced psychosis increased.

Background: This study examined the association between methamphetamine use and psychotic symptoms in a New Zealand general population birth cohort ( n = 1265 at birth)., Methods: At age 18, 21, 25, 30, and 35, participants reported on their methamphetamine use and psychotic symptoms in the period since the previous interview. Generalized estimating equations modelled the association between methamphetamine use and psychotic symptoms (percentage reporting any symptom, and number of symptoms per participant). Confounding factors included childhood individual characteristics, family socioeconomic circumstances and family functioning. Long term effects of methamphetamine use on psychotic symptoms were assessed by comparing the incidence of psychotic symptoms at age 30-35 for those with and without a history of methamphetamine use prior to age 30., Results: After adjusting for confounding factors and time-varying covariate factors including concurrent cannabis use, methamphetamine use was associated with a modest increase in psychosis risk over five waves of data (adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.03-1.72 for the percentage measure; and IRR 1.24, 95% CI 1.02-1.50 for the symptom count measure). The increased risk of psychotic symptoms was concentrated among participants who had used at least weekly at any point (adjusted OR 2.85, 95% CI 1.21-6.69). Use of methamphetamine less than weekly was not associated with increased psychosis risk. We found no evidence for a persistent vulnerability to psychosis in the absence of continuing methamphetamine use., Conclusion: Methamphetamine use is associated with increased risk of psychotic symptoms in the general population. Increased risk is chiefly confined to people who ever used regularly (at least weekly), and recently.

Background: Methamphetamine has been consistently associated with positive psychotic symptoms, but little is known about whether the reverse also occurs., Aims: This study determined whether the relationship between methamphetamine use and positive psychotic symptoms is bidirectional over 12 months. The impact of lifetime psychotic disorders and methamphetamine dependence on these relationships was also examined., Method: A total of 201 regular (at least monthly) primary methamphetamine users were recruited from free needle and syringe programmes in three Australian cities. Data on the frequency of methamphetamine and other drug use (from Timeline Followback inteviews) and the severity of positive psychotic symptoms (using the Brief Psychiatric Rating Scale) in the past 2 weeks were collected in 12 contiguous monthly face-to-face interviews (mean of 9.14/11 (s.d. = 3.16) follow-ups completed). Diagnoses were derived using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders., Results: The mean age of participants was 31.71 years (s.d. = 8.19) and 39% (n = 77) were women. At baseline 55% (n = 110) were dependent on methamphetamine and 51% (n = 102) had a lifetime psychotic disorder. Cross-lagged dynamic panel models found a significant bidirectional relationship between psychotic symptoms and methamphetamine use (Comparative Fit Index (CFI) = 0.94, standardised root mean square residual (SRMR) = 0.05, root mean square error of approximation (RMSEA) = 0.05, 95% CI 0.04-0.06). The magnitude of the relationship in each direction was similar, and the presence of methamphetamine dependence or a lifetime psychotic disorder did not have an impact on results., Conclusions: A dynamic, bidirectional relationship between methamphetamine and psychotic symptoms of similar magnitude in each direction was found over 1 year. This suggests integrated treatments that target methamphetamine, psychotic symptoms and their interrelationship may be of most benefit.

Objectives: Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA., Methods: We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%., Results: A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis., Conclusion: HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation., Trial Registration: Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Cycloserine, or its structural analogue terizidone, has been associated with neuropsychiatric toxicity (psychosis, depression, and neuropathy). Prospective clinical data on the incidence of and risk factors for neuropsychiatric toxicity in TB patients treated with cycloserine are limited., Methods: A prospective evaluation of neuropsychiatric toxicity was performed using validated screening tools in patients with multidrug-resistant tuberculosis treated with terizidone. Cox proportional hazard modelling was performed to explore the effects of clinical variables and measures of cycloserine pharmacokinetics in plasma., Results: A total 144 participants were recruited: 86 were male and 58 were female; their median age was 35.7 years and 91 (63%) were HIV-infected. Fifty-five (38%) participants developed at least one neuropsychiatric event (30 cases per 100 person-months): 50 (35%) neuropathy, 14 (10%) depression, and 11 (8%) psychosis. Neuropathy was independently associated with cycloserine clearance ((adjusted hazard ratio 0.34 (aHR), P = 0.03)) and high-dose pyridoxine (200 mg vs 150 mg daily, aHR: 2.79, P = 0.01)., Conclusions: A high incidence of early neuropsychiatric toxicity was observed in this cohort of patients treated with terizidone. Cycloserine clearance and higher doses of pyridoxine are associated with incident or worsening peripheral neuropathy., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Longitudinal studies of cannabis exposure during early adolescence in the general population frequently report an increased risk of subsequently developing psychotic symptoms or a psychotic illness. However, there is a dearth of knowledge about the effects of early cannabis exposure on psychosis in homeless and precariously housed adults, who represent a population afflicted with high rates of psychosis. The aim of the present study was to examine how early cannabis exposure (by age 15) compared to later first use (after age 15) affected the expression of adult psychosis in this population. Secondary measures of psychopathology, drug use, cognition and brain structure were also collected. 437 subjects were recruited from single room occupancy hotels in the urban setting of the Downtown Eastside of Vancouver, Canada. Psychiatric diagnoses were determined, and psychotic symptom severity was measured with the 5-factor PANSS. Participants completed a battery of neurocognitive tests, and brain structure was assessed using structural and diffusion tensor imaging MRI scans. Results indicated that early cannabis exposure was associated with an increased risk (OR = 1.09, p < .05) of developing substance induced psychosis, whereas later first use increased risk (OR = 2.19, p < .01) of developing schizophrenia or schizoaffective disorder. There was no group difference in neurocognitive function, although differences were observed in the lateral orbitofrontal cortex and white matter tract diffusivity. These findings indicate that early cannabis exposure in this population may increase the risk of developing drug associated psychoses, which could potentially be mediated in part through altered neurodevelopmental brain changes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Worldwide, cannabis is the most used illegal substance, and the use of cannabis has increased over the years. An increase in the level of tetrahydrocannabinol (THC) in cannabis has also been seen. It is currently unclear whether this has led to an increase in the incidence of cannabis-induced psychosis. We aimed to investigate (1) the development of incidence of cannabis-induced psychosis over time compared with other substance-induced psychoses and (2) the development of incident cases of cannabis-induced psychosis over time compared with dual diagnosis defined as schizophrenia and a cannabis use disorder., Method: Data on psychiatric diagnoses were extracted from the Danish Psychiatric Central Research Register and summarized per year as both absolute incidence (number of cases) and incidence rates per 100 000 person years., Results: The incidence rate of cannabis-induced psychosis increased steadily from 2.8 per 100 000 person years in 2006 to 6.1 per 100 000 person years in 2016. There was a corresponding increase in dual diagnosis with schizophrenia and cannabis use disorder, but a decrease in alcohol-induced psychosis. The data showed no trend in the other substance-induced psychosis investigated in this thesis., Conclusion: The increase in cannabis-induced psychosis follows both the increase in the level of THC in cannabis, and the increase in cannabis use. The change in diagnostic practice does not appear to explain the increase in incidence of cannabis-induced psychosis.

Introduction: In the stressful context of the coronavirus disease 2019 (COVID-19) pandemic, some reports have raised concerns regarding psychiatric disorders with the use of hydroxychloroquine. In this study, we reviewed all psychiatric adverse effects with hydroxychloroquine in COVID-19 patients, as well as in other indications, reported in VigiBase, the World Health Organization's (WHO) global database of individual case safety reports., Methods: First, we analyzed all psychiatric adverse effects, including suicide, of hydroxychloroquine in COVID-19 patients reported to 16 June 2020. We also performed disproportionality analysis to investigate the risk of reporting psychiatric disorders with hydroxychloroquine compared with remdesivir, tocilizumab, or lopinavir/ritonavir prescribed in COVID-19 patients. We used reporting odds ratios (RORs) and their 95% confidence intervals (CIs) to calculate disproportionality. Second, we sought to examine the psychiatric safety profile of hydroxychloroquine in other indications (before 2020)., Results: Among the 1754 reports with hydroxychloroquine in COVID-19 patients, we found 56 psychiatric adverse effects. Half of these adverse effects were serious, including four completed suicides, three cases of intentional self-injury, and 12 cases of psychotic disorders with hallucinations. Compared with remdesivir, tocilizumab, or lopinavir/ritonavir, the use of hydroxychloroquine was associated with an increased risk of reporting psychiatric disorders (ROR 6.27, 95% CI 2.74-14.35). Before 2020, suicide was the main cause of death among all adverse drug reactions reported with hydroxychloroquine, followed by cardiac adverse effects (cardiomyopathy) and respiratory failure., Conclusions: This pharmacovigilance analysis suggests that COVID-19 patients exposed to hydroxychloroquine experienced serious psychiatric disorders, and, among these patients, some committed suicide. Further real-world studies are needed to quantify the psychiatric risk associated with hydroxychloroquine during the COVID-19 pandemic.

The study by Moran et al. on the risk of psychosis among adolescents in the US who are treated with a stimulant for ADHD is important. This is because ADHD is a common disorder (3-5%), because psychosis often emerges in adolescence, because ADHD and psychosis share increased comorbidity and because ADHD is treated with stimulant medication that may increase the risk of psychosis. This means there is a multifactorial relationship between ADHD and psychosis.The outcome of the study is that stimulants increase the risk of psychosis to a limited extent, i.e. 0.10% for methylphenidate and 0.21% for dexamphetamine. It is recommended to opt for methylphenidate in adolescents with ADHD. This is confirmed by a Swedish registry study that controlled for a history of psychosis and showed that methylphenidate did not increase the incidence of psychosis after one year, regardless of a history of psychosis.

Cannabis is the illicit drug most commonly used worldwide, and its consumption can both induce psychiatric symptoms in otherwise healthy subjects and unmask a florid psychotic picture in patients with a prior psychotic risk. Previous studies suggest that chronic and long-term cannabis exposure may exert significant negative effects in brain areas enriched with cannabinoid receptors. However, whether brain alterations determined by cannabis dependency will lead to a clinically significant phenotype or to a psychotic outbreak at some point of an abuser's life remains unclear. The aim of this study was to investigate morphological brain differences between chronic cannabis users with cannabis-induced psychosis (CIP) and non-psychotic cannabis users (NPCU) without any psychiatric conditions and correlate brain deficits with selective socio-demographic, clinical and psychosocial variables. 3T magnetic resonance imaging (MRI) scans of 10 CIP patients and 12 NPCU were acquired. The type of drug, the frequency, and the duration, as well socio-demographic, clinical and psychosocial parameters of dependency were measured. CIP patients had extensive grey matter (GM) decreases in right superior frontal gyrus, right precentral, right superior temporal gyrus, insula bilaterally, right precuneus, right medial occipital gyrus, right fusiform gyrus, and left hippocampus in comparison to chronic cannabis users without psychosis. Finally, in CIP patients, the results showed a negative correlation between a domain of the Brief Psychiatric Rating Scale (BPRS), BPRS-Activity, and selective GM volumes. Overall, the results suggest that cannabis-induced psychosis is characterized by selective brain reductions that are not present in NPCU. Therefore, neuroimaging studies may provide a potential ground for identifying putative biomarkers associated with the risk of developing psychosis in cannabis users.

Objective: We have conducted a study to clarify the association between amphetamine-related disorders (ARD) and the risk of developing dementia., Methods: This study used a retrospective cohort design by using Taiwan's National Health Research Institute Database. A random sample of 68,300 subjects between January 1, 2000, and December 31, 2015, was obtained, comprising of 17,075 patients with ARD, and 51,225 controls without ARD (1:3), matched for gender and age group. After adjusting for covariates, a Fine and Gray's survival analysis (competing with mortality) was used to compare the risk of dementia during a 15-year follow-up period., Results: In the present study, 1,751 of 17,075 patients with ARD and 2,147 of 51,225 in the control group without ARD (883.10 vs 342.83 per 100,000 person-years) developed dementia. ARD cohort was more likely to develop dementia (hazard ratio = 4.936 [95% CI: 4.609-5.285, P < 0.001). After adjusting for gender, age groups, education, monthly insured premiums, urbanization level, geographic region, comorbidities, the hazard ratio for ARD patients was 5.034 (95% CI: 4.701-5.391, P < 0.001). ARD has been associated with overall dementia, Alzheimer dementia, vascular dementia, and other dementia. Both the amphetamine use disorder and amphetamine-induced psychotic disorders were associated with the risk of overall dementia, Alzheimer dementia, vascular dementia, and other dementia., Interpretation: This study shows that patients with ARD, both the amphetamine use disorder and the amphetamine-induced psychotic disorder, may have a nearly fivefold risk of developing dementia, including Alzheimer dementia and other types of dementia., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: To analyze the risk of megestrol, a glucocorticoid and progesterone receptor agonist used to enhance appetite, on the development of a new psychiatric diagnosis., Design and Participants: Deidentified data of megestrol (n = 706) and propensity score-matched comparison (age, gender, and body mass index) patients (n = 2,118) from January 1, 2001 to June 30, 2018 were obtained from the UT Southwestern patient database. Data were analyzed using a series of conditional binary logistic regressions controlling for comorbidities, pre-existing psychiatric disorders, and number of patient encounters., Setting: A large academic medical center database of megestrol-treated patients and matched comparison patients was used., Measurements and Results: The regression model showed that megestrol was significantly associated with developing a new psychiatric diagnosis (B = 1.28, Wald χ 21  = 83.12, odds ratio [OR] = 3.60, p <0.001). In subgroup analyses, development of cognitive (B = 2.42, Wald χ 21  = 16.09, OR = 11.30, p <0.001), mood (B = 1.31, Wald χ 21  = 40.38, OR = 3.70, p <0.001), and anxiety (B = 1.72, Wald χ 21  = 45.28, OR = 5.60, p <0.001) disorders were also associated with megestrol use., Conclusions: Patients taking megestrol were significantly more likely to develop a new psychiatric diagnosis than comparison patients. Highest risks were associated with the development of cognitive diagnoses. The findings suggest that megestrol, like other glucocorticoid agonists, is associated with an increased risk of developing a psychiatric disorder. This risk should be considered when determining the risk-to-benefit ratio of megestrol use in patients., (Published by Elsevier Inc.)

Introduction: Given the recent and impending changes to the legal status of nonmedical cannabis use in Canada, understanding the effects of cannabis use on the health care system is important for evaluating the impact of policy change. The aim of this study was to examine pre-legalization trends in hospitalizations for mental and behavioural disorders due to the use of cannabis, according to demographics factors and clinical conditions., Methods: We assessed the total number of inpatient hospitalizations for psychiatric conditions with a primary diagnosis of a mental or behavioural disorder due to cannabis use (ICD-10-CA code F12) from the Hospital Mental Health Database for ten years spanning 2006 to 2015, inclusive. We included hospitalizations from all provinces and territories except Quebec. Rates (per 100 000 persons) and relative proportions of hospitalizations by clinical condition, age group, sex and year are reported., Results: Between 2006 and 2015, the rate of cannabis-related hospitalizations in Canada doubled. Of special note, however, is that hospitalizations during this time period for those with the clinical condition code "mental and behavioural disorders due to use of cannabinoids, psychotic disorder" (F12.5) tripled, accounting for almost half (48%) of all cannabis-related hospitalizations in 2015., Conclusion: Further research is required to investigate the reasons for the increase in hospitalizations for cannabis-related psychotic disorder. The introduction of high-potency cannabinoid products and synthetic cannabinoids into the illicit market are considered as possible factors., Competing Interests: The authors have no conflicts of interest to declare.

Objective: Extrapyramidal side-effects (EPSE) are frequent in patients treated with antipsychotics and comorbid substance use disorders (SUDs). Methamphetamine has been shown to act as a dopaminergic neurotoxin. We aimed to determine whether EPSE occur more often in patients with psychotic disorders and co-occurring methamphetamine (MA) use disorders, and we examined the relationship between MA use, antipsychotic type, dose and EPSE. Methods: This study was a secondary analysis of data from three separate primary studies. Across all studies, psychiatric and SUD diagnoses were determined using the SCID-I for DSM-IV. EPSE were determined using the Simpson-Angus Scale (SAS) for Parkinsonism, the Barnes Akathisia Rating scale (BARS), and the Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia. Participants were classified as having any EPSE if they scored above the cutoff on any of the EPSE scales (SAS, BARS, AIMS). We analyzed data using multivariable logistic regression analysis. Results: The sample included 102 patients with non-affective or affective psychotic disorders. Of the total sample, 65.7% were male, 54.9% had schizophrenia spectrum disorders, 20.5% bipolar type I disorder with psychotic features, 11.7% schizoaffective disorder and 12.7% had substance-induced psychosis. A diagnosis of a methamphetamine use disorder (abuse or dependence) was present in 25.5% of participants. EPSE occurred in 38.2% of patients and were significantly associated with MA use in the unadjusted and adjusted analysis, OR adj  = 4.01, 95% CI [1.07, 14.98], p  = .039. Patients with MA dependence and MA use >3 years were significantly more likely to have EPSE. We found a significant interaction effect between MA use disorders and standardized antipsychotic dose on the occurrence of EPSE, OR adj  = 1.01, 95% CI [1.00, 1.01], p  = .042, with MA users having a disproportionally higher likelihood of having EPSE compared to MA non-users as antipsychotic dosage increased. There were no significant associations of EPSE with comorbid alcohol, cannabis, or methaqualone use disorders. Conclusions: Patients with a MA use disorder were significantly more likely to have EPSE with evidence for a dose-response effect. Clinicians should carefully titrate antipsychotic dosage from lower to higher doses to avoid EPSE in patients with MA use disorders.

Objective: Previous studies have suggested that infections increase the risk of schizophrenia. In this study, the authors aimed to investigate 1) whether infections increase the risk of substance-induced psychosis, and 2) whether infections increase the risk of converting from substance-induced psychosis to schizophrenia., Methods: The study data were drawn from the combined nationwide Danish registers and included all people born in Denmark since 1981. The authors used Cox proportional hazards regression with infections as time-varying covariates, estimating hazard ratios and 95% confidence intervals. Infections were operationalized both as any infection and by the site of infection., Results: The study included 2,256,779 individuals, for whom 3,618 cases of incident substance-induced psychosis were recorded. Any infection increased the risk of substance-induced psychosis (hazard ratio=1.30, 95% CI=1.22-1.39). For the first 2 years, the risk was doubled. Hepatitis was the infection most strongly associated with substance-induced psychosis (hazard ratio=3.42, 95% CI=2.47-4.74). Different types of infections were linked with different types of substance-induced psychosis. Most associations remained significant after controlling for potential confounders, such as substance use disorders. Only hepatitis predicted conversion to schizophrenia after substance-induced psychosis (hazard ratio=1.87, 95% CI=1.07- 3.26)., Conclusions: The study results support the hypothesis of an immunological component to psychosis.

Competing Interests: Competing interests: None declared.

Purpose: While levetiracetam (LEV) usage is a known risk factor for psychosis in epilepsy, the modulating effect of certain patient and treatment characteristics on the risk of psychosis has yet to be fully elucidated., Methods: In our tertiary epilepsy center, 84 patients with psychotic symptoms during LEV usage and 100 controls without psychotic symptoms during LEV usage were selected. Patient records were reviewed including demographics, medical history, antiepileptic drug use, and cognitive abilities. Univariate comparisons were performed, and variables with p < 0.1 were selected for binary logistic regression analysis., Results: The total incidence of psychosis during LEV therapy in our population was 3.7%. The timing of psychotic symptoms was classified as postictal in 20 (19.8%), interictal in 14 (15.4%), postepilepsy surgery in 1 (1.1%), and unknown in 18 cases (19.8%). In 31 cases (34.1%), psychotic symptoms were classified as an antiepileptic drug-induced psychotic disorder (AIPD) as a result of LEV. In 7 cases (7.7%), AIPD occurred as a result of a different antiepileptic drug. A significant association was found between the experience of psychotic symptoms and status epilepticus (p = 0.002), a history of psychotic symptoms (p < 0.000), a history of psychiatric illness other than psychosis (p = 0.010), and concomitant phenytoin (PHT) usage (p = 0.044). Cotherapy with lamotrigine (LTG) was protective (p = 0.042). A separate analysis of controls and exclusively the 31 cases with LEV-induced AIPD yielded comparable results; a significant association was confirmed with status epilepticus (p = 0.021) and history of psychotic symptoms (p = 0.018), as well as with female gender (p = 0.047) and intellectual disability (p = 0.043)., Conclusion: Our retrospective study found that psychotic symptoms during LEV therapy were significantly associated with status epilepticus, a history of psychotic symptoms, a history of psychiatric illness other than psychosis, and concomitant PHT usage, whereas concomitant LTG usage was protective. Psychotic symptoms specifically as an adverse drug reaction to LEV were significantly associated with female gender, intellectual disability, status epilepticus, and a history of psychotic symptoms., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Evidence for an association between cannabis and psychosis has been documented in literature in many forms including experimental studies, epidemiological data, and case series. The association has implications for psychotic outcomes ranging from mild to severe and occurring over minutes to years. Due to the huge variety of exposures and outcome measures reported, creating a coherent account of all the available information is difficult. A useful way to conceptualize these wide-ranging results is to consider the association between cannabis and psychosis as it occurs within the context of widely used DSM-5 diagnoses. In the present review we examine cannabis/psychosis associations as they pertain to Cannabis Intoxication, Cannabis-Induced Psychotic Disorder, and Schizophrenia. This allows for an understanding of the cannabis and psychosis association along something approaching a continuum. Cannabis intoxication becomes Cannabis-Induced Psychotic Disorder once certain severity and duration criteria are met and Cannabis-Induced Psychotic Disorder is heavily associated with future schizophrenia diagnoses.

Objective: The objective of this study was to clarify the etiology of substance-induced psychotic disorder and its progression to schizophrenia in a Swedish national sample., Methods: Individuals with a registration of substance-induced psychotic disorder between 1997 and 2015 in national medical registries (N=7,606) were followed up for a mean of 84 months. Data from medical, criminal, and pharmacy registries on first-degree through third-degree relatives were used to calculate familial risk scores for nonaffective psychosis, drug abuse, and alcohol use disorder., Results: Individuals with substance-induced psychotic disorder had large elevations in standardized familial risk scores for drug abuse (+1.09, 95% CI=1.02, 1.15) and alcohol use disorder (+0.98, 95% CI=0.93, 1.03) and modest elevations for nonaffective psychosis (+0.35, 95% CI=0.30, 0.41). The cumulative risk for progression to schizophrenia was 11.3%; it was lowest for alcohol-induced and highest for cannabis-induced psychotic disorder, and it was predicted by early age at diagnosis of substance-induced psychotic disorder, male sex, and further registrations for episodes of drug abuse, alcohol use disorder, and substance-induced psychotic disorder. A risk prediction model found that 47% of individuals who converted to schizophrenia were in the upper 20% of risk. Familial risk scores for drug abuse and alcohol use disorder did not significantly discriminate those who converted to schizophrenia from those who did not, while familial risk score for nonaffective psychosis did (0.67, 95% CI=0.40, 0.95, versus 0.33, 95% CI=0.28, 0.39). Familial risk scores for nonaffective psychosis were indistinguishable between individuals with schizophrenia with and without prior substance-induced psychosis. Assignment of early retirement by the Swedish Social Insurance Agency strongly discriminated between individuals with substance-induced psychotic disorder with and without later schizophrenia., Conclusions: Substance-induced psychotic disorder appears to result from substantial drug exposure in individuals at high familial risk for substance abuse and moderately elevated familial risk for psychosis. Familial risk for psychosis, but not substance abuse, predicts progression from substance-induced psychosis to schizophrenia. Schizophrenia following substance-induced psychosis is likely a drug-precipitated disorder in highly vulnerable individuals, not a syndrome predominantly caused by drug exposure.

Background: There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder., Methods: In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12-30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis., Findings: We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38·7%) individuals were assessed and 37 916 (61·3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2·0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1·04 (95% CI 0·80-1·34) in adolescents and young adults without a history of psychosis and 0·95 (0·69-1·30) among those with a history of psychosis., Interpretation: Contrary to clinical concerns, we found no evidence that initiation of methylphenidate treatment increases the risk of psychotic events in adolescents and young adults, including in those individuals with a history of psychosis. Our study should reassure clinicians considering initiating methylphenidate treatment for ADHD in adolescents and young adults, and it challenges the widely held view in clinical practice that methylphenidate should be avoided, or its use restricted, in individuals with a history of psychosis., Funding: Swedish Research Council, National Institute of Mental Health, UK National Institute of Health Research Nottingham Biomedical Research Centre., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To identify the prevalence and profile of amphetamine-type-substance-related presentations to the Emergency Department Mental Health Team of a local health district in Australia., Methods: Data was collected from medical records of all amphetamine-type-substance presentations to the Emergency Department Mental Health Team over a 1-year period, between 1 January 2015 and 31 December 2015., Results: Of all presentations referred to the Emergency Department Mental Health Team, 0.15% ( N  = 189) were amphetamine-type-substance related. Of these, the majority were male, the average age was 32, 19.0% engaged in intravenous drug use, some were aggressive and 15.9% required tranquilisation. The most common presenting issues were psychosis and suicidal threats, intent and behaviour (including intentional overdose). Multiple comorbid conditions were identified. On discharge, 34.4% were admitted into a psychiatric hospital and 32.8% were referred to Community Mental health teams., Conclusions: Amphetamine-type-substance users suffer from multiple comorbidities and pose a significant burden on emergency services.

Objective: Many studies show psychoses after some antiepileptic drug (AED) administrations (post-AED administration psychoses [PAP]). It remains uncertain about psychogenetic potential of each AED and effects of clinical state factors on PAP. We examined the relations between AED-related factors (types, generations, dosages, and concomitant AED) and PAP., Methods: The clinical records of patients with focal epilepsy were retrospectively reviewed from eight adult epilepsy clinics, for every six-month period after administration of a new drug (either AED or non-AED) between 1981 and 2015. Characteristics of psychotic episodes, AED-related factors (type, daily dosage, and concomitant AED), and other state-related risk factors to psychosis (age, duration of epilepsy, history of psychosis, and seizure frequency) were examined. Psychogenetic risks of AED-related and state-related factors were analyzed with multifactorial procedures., Results: Of 2067 patients with focal epilepsy, 5018 new drugs (4402 AEDs and 616 non-AEDs) were administered. Within the first six-month period, 89 patients exhibited 105 psychotic episodes (81 interictal and 24 postictal psychoses: 55 first episodes and 50 recurrences). With second-generation AED (SAED) administration, particularly topiramate and lamotrigine, frequency of psychosis was significantly increased. Daily dosage of AED was not significantly associated with psychosis. Psychosis tended to occur with a higher number of concomitant AED. Subsequent analysis with AED-related and general factors showed that SAED administrations and previous psychotic history were the most significant risks for PAP., Conclusion: Post-AED administration psychoses is associated with type of AED (SAED), rather than its dosage. Individual vulnerabilities are also associated with PAP., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: To examine the relationship between a regional economic downturn (indicated by the rise of population unemployment rate) and the rate of psychoactive-substance-induced psychiatric hospital admissions in the population in a rural/regional setting., Methods: Hospital admission records from January 2013 to December 2016 were reviewed retrospectively. All patients with admissions to the Mackay inpatient psychiatric unit with diagnosis of mental and behavioural disorders due to psychoactive substance use were recorded using (ICD-10) F10-F19 codes. The relationship between the regional unemployment rate and the hospital admission rate was analysed using linear regression analysis., Results: A statistically significant regression was found (F(1,46) = 39.46, p < 0.0001), R 2  = 0.46). The predicted number of admissions per 100,000 population in a month was observed to increase on average by 3.13 per month (95% CI = 2.12-4.13, p < 0.0001) for each percentage increase in the regional unemployment rate., Conclusions: There was a statistically significant association between the population unemployment rate and the rate of substance induced psychiatric hospital admissions. Implications for regional Australian service provision and unmet needs were discussed. Further research is required to confirm this observation.

Background: Current evidence suggests that women are more sensitive to the effects of cannabinoids. The aim of this study was to investigate the relevance of sex in the association of synthetic cannabinoid (SC) use with psychosis and agitation., Methods: A retrospective chart review was conducted for patients admitted to a psychiatric unit (2014-2016) to extract information on demographic factors, use of substances, clinical symptoms, and pharmacologic treatments. Study groups were defined as SC users (anyone who reported use of SCs over the past 3 months), cannabis users (positive toxicology screen for Δ⁹-tetrahydrocannabinol [THC]), and controls (those who denied use of SCs over the past 3 months and had negative toxicology for THC)., Results: Digital charts of 983 patients were reviewed. A total of 162 subjects reported use of SCs over the past 3 months (76% male), and 292 subjects had positive toxicology screen for THC (67% male). A total of 38.9% of SC users (n = 63) had positive urine toxicology screen for THC. SC users had higher risks of psychotic presentations (adjusted odds ratio [AOR] = 3.390; 95% CI, 1.390-8.267) and agitation (AOR = 4.643; 95% CI, 1.974-10.918) compared to the controls. While women had lower rates of psychosis than men in the cannabis and control groups, the rates were markedly potentiated with SC use to high levels (79%) approximately equal to that seen in men (80%). There was also a significant interaction between SC use and sex for agitation (AOR = 0.308; 95% CI, 0.117-0.808). Female SC users were significantly more agitated than male SC users (73.7% vs 47.6%, respectively, P = .005)., Conclusions: SC users are more likely than nonusers to be psychotic or agitated in an inpatient setting. The potentiated rates of psychosis and agitation with SC use in women suggest that they may have a greater sensitivity to these synthetic compounds.​., (© Copyright 2019 Physicians Postgraduate Press, Inc.)

Background: Kratom is a traditional medicinal herb widely used in Malaysia and Thailand. Despite its widespread use and statements by regulatory agencies on the potential for kratom-associated psychosis, there is little data regarding the prevalence of psychotic symptoms among kratom users. This study investigated the prevalence of psychosis among kratom users, described psychotic symptomatology and severity, while examining associations between kratom use characteristics and the occurrence of psychotic symptoms., Methods: This cross-sectional clinical survey recruited 150 regular kratom users. The Mini International Neuropsychiatric Interview (MINI) and Diagnostic and Statistical Manual of Mental Disorders 5 th Edition (DSM-V) diagnostic criteria were used to evaluate psychotic symptomatology among kratom users, and the Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of psychiatric symptoms. Chi-square tests with Yate's correction were performed to determine the association between kratom use characteristics and the occurrence of psychotic symptoms among kratom users in this study., Results: Six out of 150 kratom users (4%) presented with any psychotic symptoms. The psychotic symptoms reported were positive symptoms and thought alienation, with a mean BPRS score of 33 (i.e., mild severity). Variables related to kratom use (such as intake of kratom with diphenhydramine, duration of kratom use, and quantity and frequency of daily kratom use) were not associated with the occurrence of psychotic symptoms among kratom users., Conclusion: Although psychotic symptoms could occur among regular kratom users, they were rare and not significantly associated with kratom use characteristics. We found no evidence of elevated psychosis among regular users., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Khat is an amphetamine like psychostimulant chewed by over 10 million people globally. Khat use is thought to increase the risk of psychosis among its chewers. The evidence around this however remains inconclusive stemming from the scanty number of studies in this area and small study sample sizes. We undertook a large household survey to determine the association between psychotic symptoms and khat chewing in a rural khat growing and chewing population in Kenya., Methods: For this cross-sectional household survey, we randomly selected 831 participants aged 10 years and above residing in the Eastern region of Kenya. We used the psychosis screening questionnaire (PSQ) to collect information on psychotic symptoms and a researcher designed sociodemographic and clinical questionnaire to collect information on its risk factors. We used descriptive analysis to describe the burden of khat chewing and other substance use as well as rates and types of psychotic symptoms. Using a univariate and multivariate analyses with 95% confidence interval, we estimated the association between khat chewing and specific psychotic symptoms., Results: The prevalence of current khat chewing in the region was at 36.8% (n = 306) with a male gender predominance (54.8%). At least one psychotic symptom was reported by 16.8% (n = 168) of the study population. Interestingly, psychotic symptoms in general were significantly prevalent in women (19.5%) compared to men (13.6%) (p = 0.023). Khat chewing was significantly associated with reported strange experiences (p = 0.024) and hallucinations (p = 0.0017), the two predominantly reported psychotic symptoms. In multivariate analysis controlling for age, gender, alcohol use and cigarette smoking, there was a positive association of strange experiences (OR, 2.45; 95%CI, 1.13-5.34) and hallucination (OR, 2.08; 95% C.I, 1.06-4.08) with khat chewing. Of note was the high concurrent polysubstance use among khat chewers specifically alcohol use (78.4%) and cigarette smoking (64.5%)., Conclusions: Psychotic symptoms were significantly elevated in khat users in this population. Future prospective studies examining dose effect and age of first use may establish causality.

Background: Substance induced psychotic disorders (SIPD) have been historically considered as associated with better clinical and functional outcomes than other psychotic diagnoses. As a result, treatments for those with SIPD are often considerably less intensive, yet this is not based on evidence. The present study aimed to examine whether differences exist between those with SIPD and other first episode psychosis (FEP) diagnoses in regards to demographic and clinical factors, and to determine the symptomatic, clinical and functional outcomes in those with SIPD., Methods: This study included all young people aged 15-24 who presented with a FEP to the Early Psychosis Prevention and Intervention Centre between 01/01/2011 and 31/12/2013. Group differences were analysed with independent samples t-tests and chi-square analyses and equivalent non-parametric tests as appropriate. Where applicable, odds ratios were calculated., Results: 544 young people presented with a FEP and 10.3% (N = 56) were diagnosed with SIPD. Individuals with SIPD were more likely to be male, unemployed, and have a comorbid substance use disorder. There were no significant differences between groups regarding duration of untreated psychosis, severity of psychotic symptoms, time to remission, or rates of relapse. Those with SIPD were less likely to be employed or engaged in study at discharge and 35.7% of those with SIPD had a change of diagnosis to a schizophrenia spectrum or bipolar disorder after a median of 84 weeks., Conclusion: Young people diagnosed with SIPD should be an important focus of early intervention services and receive comparable treatment to those with other psychotic diagnoses., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit-hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied., Methods: We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases., Results: We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09)., Conclusions: Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. (Funded by the National Institute of Mental Health and others.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: Evidence suggests that cannabis-induced psychotic-like experiences may be a marker of psychosis proneness. The effect of such experiences on cannabis use has not systematically been examined., Methods: We undertook a mixed-methods online survey of 1231 cannabis users (including 926 continued users) using the Cannabis Experiences Questionnaire. We examined the effect of psychotic-like and pleasurable experiences on cessation of cannabis and intention to quit. Socio-demographic variables, cannabis use parameters and substance misuse history were included as covariates. Free-text data explored subjective reasons for changes in use., Results: Cessation of cannabis use was associated with greater psychotic-like experiences [p &lt; 0.001, Exp(B) 1.262, 95% confidence interval (CI) 1.179-1.351], whilst continued cannabis users were more likely to report pleasurable experiences [p &lt; 0.001, Exp(B) 0.717, 95% CI 0.662-0.776]. Intention to quit cannabis in continued users was associated with greater psychotic-like experiences [p &lt; 0.003, Exp(B) 1.131, 95% CI 1.044-1.225], whilst intention to not quit was significantly associated with increased pleasurable experiences [p &lt; 0.015, Exp(B) 0.892, 95% CI 0.814-0.978]. Whereas former users clearly ascribed cessation to negative experiences, continued users who expressed intention to quit less readily ascribed the intention to negative experiences., Conclusions: Elucidation of psychotic-like experiences may form the basis of a therapeutic intervention for those who wish to quit. Cessation in those with cannabis-induced psychotomimetic experiences may offset the risk for the development of a psychotic disorder, in this higher risk group.

Aim: Epidemiological data have provided evidence that psychotic-like experiences (PLEs) can occur in the general population, not necessarily accompanied by the impairment and suffering observed in formal psychiatric diagnoses. According to the psychosis continuum hypothesis, PLEs would be subject to the same risk factors as frank psychosis. The aim of this review was to summarize observational studies that evaluated cannabis use as a risk factor for PLEs as determined by the Community Assessment of Psychic Experiences in non-clinical samples. The instrument composed of 3 dimensions-positive, negative and depressive-is a scale specifically designed to assess the occurrence, frequency and impact of PLEs in non-clinical population., Methods: We searched PubMed/Medline, Web of Science and PsycInfo electronic databases for indexed peer-reviewed studies published until September 2017., Results: We initially identified 100 articles. The PRISMA model for systematic reviews was used and 19 full-text articles were analysed. In general, the findings suggested that the higher the cannabis use and the younger the participants, the higher the reports of PLEs, although associations were more consistent for the positive dimension., Conclusions: More attention should be paid to the understanding of the risk factors of PLEs in the general population, since these experiences are themselves a risk for psychotic disorders., (© 2018 John Wiley & Sons Australia, Ltd.)

Synthetic cannabinoid receptor agonists (SCRAs) are suggested to have increased potential to induce psychosis compared to natural cannabis (NC). In this review we synthesise current knowledge about the association of SCRA use with psychotic symptoms. Following a literature search we identified 2 toxicology reports, 4 case-control studies, 3 cross-sectional studies and 15 case reports. In each of the case reports, we identified the presence or absence of symptoms based on the items of the Postitive and Negative Syndrome Scele (PANSS). The toxicology reports highlighted the main presenting features as being toxic psychosis and delirium (40%), agitation (10%) and hallucinations (4-7%). The median age was 25 years, and around 80% cases were male. Cross-sectional studies reported that SCRA use was present in approximately 10-13% patients presenting to acute psychiatric services, and was often the cause of their presentation, and that psychotic symptoms were present in 15% patients attending emergency departments following SCRA use. Case-control studies reported that SCRA use was significantly associated with psychotic symptoms and that SCRA users had higher levels of positive psychotic symptoms than NC users. The case reports supported the association of SCRA use with a wide range of positive and negative psychotic symptoms as well as with self-harm, agitation and aggressive behaviour. SCRA use is relatively prevalent in patients with psychosis and may lead to psychotic symptoms in individuals with no past psychiatric history. Further work is required to understand the long term risks of SCRA use and optimal management strategies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Amphetamine use and availability have increased in Australia and there are concerns that this has led to more frequent hospital admissions with amphetamine-related psychosis. This study examines whether amphetamine-related admissions to mental health units are more common at times of greater amphetamine availability., Methods: We conducted an ecological study using aggregate crime and health service data for NSW, Australia, from January 2000 to March 2015. Amphetamine-related criminal incidents (arrests or cautions for possession or use) were used as an indirect measure of amphetamine availability. Semiparametric time series analysis was used to compare monthly arrest rates to monthly hospitalisation rates for (1) amphetamine abuse or dependence, (2) amphetamine-related psychosis and (3) any psychosis., Results: Amphetamine-related admissions to NSW mental health units have increased four- to fivefold since 2009 and comprised approximately 10% of all admissions to these units in early 2015. There was a significant association between arrests and amphetamine-related admissions. After adjustment for seasonal variation, this effect demonstrated a time lag of 1-2 months. There was no relationship between amphetamine arrests and overall admissions for psychosis., Conclusion: Greater amphetamine availability significantly predicts admissions for amphetamine use disorders and amphetamine-related psychosis. Better treatment strategies are needed to break the nexus between drug availability and drug-related harm.

Synthetic cannabinoid (SC) products have gained popularity as abused drugs over the past decade in many countries. The SCs broadly impact psychological state (e.g., mood, suicidal thoughts and psychosis) and physiological functions (e.g., cardiovascular, gastrointestinal and urinary). This review is about the effects of SCs on psychotic symptoms in clinical settings and the potentially relevant chemistry and mechanisms of action for SCs. Induction of psychotic symptoms after consuming SC products were reported, including new-onset psychosis and psychotic relapses. The role of SCs in psychosis is more complex than any single chemical component might explain, and these effects may not be a simple extension of the typical effects of cannabis or natural cannabinoids., (Copyright © 2018. Published by Elsevier B.V.)

There is little consensus regarding the prevalence of methamphetamine-induced psychotic disorder (MIPD). A search of the literature was performed, effect size estimates were calculated with event rates and were aggregated with a random-effects model. Seventeen studies were included in the meta-analysis, resulting in a composite event rate of 36.5%. The event rate of MIPD was significantly higher when the period of assessment was lifetime (42.7%) and when only individuals with methamphetamine use disorders (MUD) (43.3%) were included. The prevalence of MIPD in the reviewed studies is elevated. These results highlight the need for detection and prevention strategies, and population studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Despite research showing higher use of amphetamine-type stimulants (ATS) in rural areas, limited research has examined the epidemiology of ATS-related presentations and admissions to remote regional centres. To determine the epidemiology of ATS-related (a) Emergency Department (ED) presentations and (b) inpatient admissions over a five-year period at the Hedland Health Campus (HHC) in remote Western Australia., Methods: A retrospective review of medical records was conducted. Demographic data including gender, age and indigenous status were captured., Results: Four hundred and eighty-two ATS-related hospital presentations were identified during the study period. The most common reason for ED presentation was mental and behavioural problems. Of those presenting, 66% were male and 69% identified as Aboriginal. ATS-related ED presentations increased seven-fold over the study period. Ninety-nine ATS-related inpatient admissions were identified during the study period. Psychotic disorder was the most common reason for admission. Males made up 75% of admissions and 53% identified as Aboriginal., Conclusions: This study showed a disproportionally high burden of ATS-related harm among Aboriginal people. The number of ATS-related ED presentations and inpatient admissions increased significantly over the study period.

Introduction: Isotretinoin, previously marketed as Accutane®, is an oral retinoid medication that is used to treat acne and other cutaneous disorders. Although the data is conflicting, previous reports suggest a causal relationship between isotretinoin and depression. When reviewing these previous reports, many patients who were diagnosed as "depressed" did not undergo a thorough psychiatric evaluation and/or were not diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM). These patients reported agitation, irritability, sleep disturbances, and aggression. We hypothesize that some patients previously reported as "depressed" may have been "misdiagnosed" and were actually experiencing symptoms of mania, mixed mood (depression and mania at the same time), or psychosis., Evidence Acquisition: An Ovid Medline and PubMed literature search of English language articles was performed using the keywords "isotretinoin", "retinoids", "mood", "psychiatric", "depression", "elevation", "bipolar", and "psychosis". Eleven case reports, three case series, three retrospective chart reviews, five drug registries, and two prospective studies were reviewed., Evidence Synthesis: We found that many of the patients labeled as "depressed", had signs of activation, agitation, elevated mood, and psychosis. We believe that many of these patients were most likely having manic or mixed mood episodes. These symptoms appeared to be more prevalent in patients with a personal or family history of mental illness., Conclusions: Isotretinoin may cause mood instability in both directions - depression and mania - especially in a predisposed population. With this in mind, we urge clinicians prescribing isotretinoin to focus on all psychiatric symptoms (not just depression) including mania, mixed mood, and psychosis, paying particular attention to individuals who have a personal or family history of psychiatric disease.

This study examines whether illicit amphetamine use is associated with differences in the prevalence of specific psychiatric symptoms in a community sample of individuals diagnosed with schizophrenia or affective psychotic disorders. Data was drawn from the Australian Survey of High Impact Psychosis. The Diagnostic Interview for Psychosis was used to measure substance use and psychiatric symptoms. Participants had used amphetamine within their lifetime and had an ICD-10 diagnosis of schizophrenia (n = 347) or an affective psychotic disorder (n = 289). The past year prevalence of psychiatric symptoms was compared among those who had used amphetamine in the past year (past-year use, 32%) with those who had not (former use, 68%). Univariate logistic regression analysis indicated that past-year users with schizophrenia had a significantly higher past year prevalence of hallucinations, persecutory delusions, racing thoughts, dysphoria, and anhedonia relative to former amphetamine users with schizophrenia. There were no significant differences in symptoms between past-year and former users with affective psychotic disorders. The relationship between amphetamine use and specific psychiatric symptoms varies across different psychotic disorders. Amphetamine use may hinder prognosis by exacerbating symptoms of schizophrenia through dopaminergic dysfunctions or depressive vulnerabilities, however, this needs to be confirmed by prospective longitudinal research., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims and Objectives: To review the clinical impact methamphetamine has on emergency departments by assessing the available research on the rates and features of methamphetamine-related presentations., Background: Globally, methamphetamine availability, distribution and use have rapidly increased. As a result, the number of methamphetamine-related presentations to emergency departments has also increased. In this context, it is timely to review the rate and features of methamphetamine-related presentations to understand the impact of methamphetamine on emergency departments and facilitate the allocation of services, staff and resources., Design: An integrative literature review., Methods: This study presents an integrated literature review, following the systematic review process as outlined in the PRISMA flow chart. Several databases were searched using a combination of search terms. Articles were measured against inclusion and exclusion criteria, and the final ten articles were subjected to quality appraisal and outcomes reported., Results: Methamphetamine accounted for 2.3% or less of all emergency departments presentations. The majority of methamphetamine users presenting to emergency departments were males, with a mean age 31-37. Methamphetamine-related presentations to emergency departments were more likely to present with trauma, psychosis, and be placed on 24-hr psychiatric hold. Methamphetamine-related presentations were more likely to present with agitation, aggression and homicidal behaviour and present to emergency departments out of hours and accompanied by police compared with other emergency departments substance-related presentations., Conclusions: Several important themes were highlighted in this review that has an impact on emergency departments services, resources and staff. Understanding the rate and patterns of methamphetamine-related presentations can help to provide evidence for policy development and staff education in emergency departments., Relevance to Clinical Practice: Methamphetamine-related presenters are more aggressive and agitated and more likely to be brought in by police. There is a need for policy development and staff training around these issues and further research in this area using stronger study designs., (© 2018 John Wiley & Sons Ltd.)

Objective: Chronic methamphetamine use is commonly associated with the development of psychotic symptoms. The predictors and correlates of methamphetamine-associated psychosis are poorly understood. We sought to systematically review factors associated with psychotic symptoms in adults using illicit amphetamine or methamphetamine., Methods: A systematic literature search was performed on MEDLINE (OVID), PsycINFO and EMBASE databases from inception to 8 December 2016. The search strategy combined three concept areas: methamphetamine or amphetamine, psychosis and risk factors. Included studies needed to compare adults using illicit methamphetamine or amphetamine, using a validated measure of psychosis, on a range of risk factors. Of 402 identified articles, we removed 45 duplicates, 320 articles based on abstract/title and 17 ineligible full-text articles, leaving 20 included studies that were conducted in 13 populations. Two co-authors independently extracted the following data from each study: country, setting and design; participant demographic and clinical details; sample size; measure/s used and measures of association between psychosis outcomes and risk factors. Individual study quality was assessed using a modified Newcastle-Ottawa Scale, and strength of evidence was assessed using GRADE criteria., Results: Frequency of methamphetamine use and severity of methamphetamine dependence were consistently found to be associated with psychosis, and sociodemographic factors were not. There was inconsistent evidence available for all other risk factors. Individual study quality was low-moderate for the majority of studies. Heterogeneity in study outcomes precluded quantitative synthesis of outcomes across studies., Conclusion: The most consistent correlates of psychotic symptoms were increased frequency of methamphetamine use and dependence on methamphetamine. The findings of this review highlight the need for targeted assessment and treatment of methamphetamine use in individuals presenting with psychosis.

Objective: To measure the incidence and risk factors for fluoroquinolone (ciprofloxacin, moxifloxacin, and levofloxacin)-associated psychosis or delirium in a veteran population., Methods: A retrospective study was conducted in the Western New York Veterans Affairs Health System (2005-2013). Participants were hospitalized veterans receiving a fluoroquinolone for at least 48 hours (n = 631). Cases of delirium or psychosis were defined by the Diagnostic and Statistical Manual of Mental Disorders-IV criteria, and the Naranjo scale (score ≥ 1) was used to determine the probability of the adverse drug reaction being related to fluoroquinolones. A bivariate analysis of covariates followed by a multivariate logistic regression was used to determine predisposing factors to the development of delirium/psychosis., Results: The mean age of the population was 71.5 years (range: 22-95). Fluoroquinolone-associated delirium/psychosis occurred in 3.7% of the inpatients studied (n = 23). The median Naranjo score was 3 indicating a possible association. Psychosis/delirium occurred in 3.6% of ciprofloxacin-treated patients (n = 14/391), 4.5% of patients-treated with moxifloxacin (n = 9/200), and 0% of those receiving levofloxacin (n = 0/40); p = 0.4. Significant risk factors for development of delirium/psychosis in patients receiving a fluoroquinolone in the multivariate logistical regression included typical antipsychotic use (OR, 5.4; 95% CI: 1.4-16.7) and age. A 10-year increase in age was associated with a 1.8-fold greater odds of a neuropsychiatric event., Conclusions: Fluoroquinolones may be more commonly associated with delirium/psychosis than originally reported in this veteran population. Caution should be used when prescribing a fluoroquinolone for patients on typical antipsychotics and those of advanced age., (Published by Elsevier Inc.)