Steroid-induced psychosis: a spectrum of neuropsychiatric glucocorticoid side effects.

Glucocorticoid-induced neuropsychiatric side effects have been known since their initial usage and frequently manifest in clinical settings. Despite this, they remain unpredictable, variable and complex to manage, impacting patient outcomes and the healthcare system.We report a case of glucocorticoid-induced psychosis after the administration of dexamethasone post-neurosurgical intervention and its evolution with the initiation of chemotherapy. Although initially manic symptoms were prominent, with the beginning of chemotherapy psychotic symptoms dominated the clinical presentation, followed by depressive symptoms. Despite challenges in diagnosis and management, including adverse reactions to antipsychotic treatment, this case provides critical insights into the variable and dynamic nature of neuropsychiatric side effects induced by glucocorticoids.

Incident psychotic experiences following self-reported use of high-potency cannabis: Results from a longitudinal cohort study.

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.

Betaine prevents and reverses the behavioral deficits and synaptic dysfunction induced by repeated ketamine exposure in mice.

As an N-methyl-D-aspartate (NMDA) receptor inhibitor, ketamine has become a popular recreational substance and currently is used to address treatment-resistant depression. Since heavy ketamine use is associated with persisting psychosis, cognitive impairments, and neuronal damage, the safety of ketamine treatment for depression should be concerned. The nutrient supplement betaine has been shown to counteract the acute ketamine-induced psychotomimetic effects and cognitive dysfunction through modulating NMDA receptors. This study aimed to determine whether the adjunctive or subsequent betaine treatment would improve the enduring behavioral disturbances and hippocampal synaptic abnormality induced by repeated ketamine exposure. Mice received ketamine twice daily for 14 days, either combined with betaine co-treatment or subsequent betaine post-treatment for 7 days. Thereafter, three-chamber social approach test, reciprocal social interaction, novel location/object recognition test, forced swimming test, and head-twitch response induced by serotonergic hallucinogen were monitored. Data showed that the enduring behavioral abnormalities after repeated ketamine exposure, including disrupted social behaviors, recognition memory impairments, and increased depression-like and hallucinogen-induced head-twitch responses, were remarkably improved by betaine co-treatment or post-treatment. Consistently, betaine protected and reversed the reduced hippocampal synaptic activity, such as decreases in field excitatory post-synaptic potentiation (fEPSP), long-term potentiation (LTP), and PSD-95 levels, after repeated ketamine treatment. These results demonstrated that both co-treatment and post-treatment with betaine could effectively prevent and reverse the adverse behavioral manifestations and hippocampal synaptic plasticity after repeated ketamine use, suggesting that betaine can be used as a novel adjunct therapy with ketamine for treatment-resistant depression and provide benefits for ketamine use disorders.

Forced normalization of Lennox-Gastaut syndrome using lacosamide: A case report.

PURPOSE: Forced normalization (FN) indicates psychotic episodes associated with seizure remission and disappearance of epileptiform activity on EEG. FN is likely to occur when frequent seizures are abruptly terminated by anti-epileptic drugs (AEDs) or epilepsy surgery. METHODS: We describe an atypical case of a patient with FN induced by lacosamide (LCM). RESULTS: A 23-year-old female patient with Lennox-Gastaut syndrome (LGS) was administered AEDs for LGS and hospitalised with weight loss and abnormal behaviour. Her condition fulfilled the FN criteria, which was considered to be induced by LCM. After a reduction in LCM dose, her abnormal behaviour and appetite improved. During LCM use, the patient developed no seizures, and the high amplitude diffuse sharp and slow wave complexes that were frequently observed before LCM disappeared on EEG. The LCM dose was tapered to 150 mg per day, and she became calmer with socially appropriate behaviours, although a few mild focal seizures relapsed. CONCLUSION: LCM was effective for treating LGS in this patient and induced FN. Initially, it was difficult to recognise FN in cases of psychiatric disorders, especially in patients with intellectual disability. Patients with FN induced by LCM are rare, and only four patients have been previously reported who were treated by antipsychotic drug for psychosis.

Psychiatric Disorders and Hydroxychloroquine for Coronavirus Disease 2019 (COVID-19): A VigiBase Study.

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.

Psychiatric symptoms caused by cannabis constituents: a systematic review and 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 Δ9-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.

Catatonia in Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis Misdiagnosed as Schizophrenia.

Anti-N-Mmethyl-D-aspartate receptor encephalitis is an autoimmune disease of the central nervous system with prominent neurologic and psychiatric features. Symptoms appear progressively and sometimes with an exclusively psychiatric initial presentation. The patient's evaluation should be meticulous, and we should use all the diagnostic tests required for the exclusion of entities that can mimic this disease. We report the diagnostic investigation of a case of anti-N-methyl-D-aspartate receptor encephalitis in a patient with a previous diagnosis of schizophrenia with poor response to antipsychotics. The aim of this case report is to highlight the importance of close surveillance for neuropsychiatric symptoms, especially catatonia, and to recognize autoimmune encephalitis in the differential diagnosis of psychotic disorders with neurological symptoms and resistance or intolerance to antipsychotics. A prompt diagnosis will contribute to a faster onset of therapy and an overall improvement in prognosis.

A encefalite anti-receptor N-metil-D-aspartato é uma doença auto-imune do sistema nervoso central com características neurológicas e psiquiátricas proeminentes. Os sintomas surgem progressivamente e por vezes com uma apresentação inicial exclusivamente psiquiátrica. A avaliação do doente deve ser meticulosa e devem ser realizados todos os meios complementares de diagnóstico necessários à exclusão das entidades que podem mimetizar aquela patologia. Apresenta-se a evolução diagnóstica de um caso de encefalite anti-receptor N-metil-D-aspartato num doente com diagnóstico prévio de esquizofrenia sem resposta à terapêutica anti-psicótica. Pretende-se com este caso realçar a importância de uma vigilância apertada para sintomas neuropsiquiátricos, especialmente no caso de catatonia, e de ter em consideração as encefalites auto-imunes no diagnóstico diferencial de quadros psicóticos associados a sintomas neurológicos e resistência ou intolerância a anti-psicóticos. Um diagnóstico célere contribuirá para a instituição de terapêutica atempadamente e uma melhoria global do prognóstico.

Emergencies and critical issues in Parkinson's disease.

Complications from Parkinson's disease may develop over the disease course, sometimes unexpectedly, and require prompt or even urgent medical intervention. The most common are associated with aggravation of motor symptoms; serious non-motor complications, such as psychosis, orthostatic hypotension or sleep attacks, also occur. Here we review such complications, their clinical presentation, precipitating factors and management, including those related to using device-aided therapies. Early recognition and prompt attention to these critical situations is challenging, even for the Parkinson's disease specialist, but is essential to prevent serious problems.

Risk factors predisposing to psychotic symptoms during levetiracetam therapy: A retrospective study.

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.

Trend level gene-gender interaction effect for the BDNF rs6265 variant on age of onset of psychosis.

A BDNF rs6265 [A/A] by gender by cannabis use interaction has been associated with age of onset of psychosis (AoP). We examined the gender and cannabis use-adjusted association between BDNF rs6265 [G>A] and AKT1 rs2494732 [T>C] and AoP. Data from 167 Caucasians on AoP and age at first regular cannabis use were collected. Kaplan-Meier and Cox regression analyses were conducted. A trend level gene-gender interaction effect was observed for the BDNF rs6265 A/A genotype, controlling for age at first regular cannabis use. Larger collaborative research projects are required to further investigate this effect.

Khat use and psychotic symptoms in a rural Khat growing population in Kenya: a household survey.

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.

Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study.

Background: Little is known about the relative harms of edible and inhalable cannabis products. Objective: To describe and compare adult emergency department (ED) visits related to edible and inhaled cannabis exposure. Design: Chart review of ED visits between 1 January 2012 and 31 December 2016. Setting: A large urban academic hospital in Colorado. Participants: Adults with ED visits with a cannabis-related International Classification of Diseases, Ninth or 10th Revision, Clinical Modification (ICD-9-CM or ICD-10-CM), code. Measurements: Patient demographic characteristics, route of exposure, dose, symptoms, length of stay, disposition, discharge diagnoses, and attribution of visit to cannabis. Results: There were 9973 visits with an ICD-9-CM or ICD-10-CM code for cannabis use. Of these, 2567 (25.7%) visits were at least partially attributable to cannabis, and 238 of those (9.3%) were related to edible cannabis. Visits attributable to inhaled cannabis were more likely to be for cannabinoid hyperemesis syndrome (18.0% vs. 8.4%), and visits attributable to edible cannabis were more likely to be due to acute psychiatric symptoms (18.0% vs. 10.9%), intoxication (48% vs. 28%), and cardiovascular symptoms (8.0% vs. 3.1%). Edible products accounted for 10.7% of cannabis-attributable visits between 2014 and 2016 but represented only 0.32% of total cannabis sales in Colorado (in kilograms of tetrahydrocannabinol) during that period. Limitation: Retrospective study design, single academic center, self-reported exposure data, and limited availability of dose data. Conclusion: Visits attributable to inhaled cannabis are more frequent than those attributable to edible cannabis, although the latter is associated with more acute psychiatric visits and more ED visits than expected. Primary Funding Source: Colorado Department of Public Health and Environment.

Systemic Absorption and Side Effects of Locally Injected Glucocorticoids.

Local glucocorticoid injections are often used to treat joint, soft tissue, or spinal pain, but the systemic side effects associated with these injections are poorly understood and not well recognized. There are significant known risks to systemic administration of glucocorticoids. However, there are no guidelines that address issues of systemic absorption, overall systemic risks, or other side effects of locally injected glucocorticoids. For this review, a literature search was performed, and the available evidence on systemic absorption and clinical side effects of intra-articular and epidural glucocorticoids was synthesized. The goal was to improve clinical understanding of risks associated with these injections. Existing data suggest there is significant individual variability in the amount of systemic absorption and clinical effects of locally injected glucocorticoids. However, it is clear that both intra-articular and epidural injections can have systemic effects for weeks and that complications may be associated with their use, including Cushing syndrome, loss of bone density, infection, and hyperglycemia. The concurrent use of oral steroids, the number of injections, and the type and dose of glucocorticoids used all are important considerations in estimating risks. The total dose calculation of cumulative glucocorticoid exposure should include all local injections. Caution should be exercised when local glucocorticoid injections are used in higher risk patients, such as postmenopausal women, people with diabetes, and those considering surgery in the near term. Better provider awareness of possible systemic risks should improve decision making and informed consent with patients when considering intra-articular and epidural steroid injections for painful conditions. LEVEL OF EVIDENCE: IV.

Psychological effects of dopamine agonist treatment in patients with hyperprolactinemia and prolactin-secreting adenomas.

Background Dopamine agonists (DAs) are the main treatment for patients with hyperprolactinemia and prolactinomas. Recently, an increasing number of reports emphasized DAs' psychological side effects, either de novo or as exacerbations of prior psychiatric disease. Methods Review of prospective and retrospective studies (PubMed 1976, September 2018) evaluating the psychological profile of DA-treated patients with hyperprolactinemia and prolactinomas. Case series and case reports of psychiatric complications were also reviewed. Results Most studies were cross-sectional and had a control group of healthy volunteers or patients with nonfunctioning pituitary adenomas. There were few prospective studies, with/without control group, that included small numbers of patients. Compared with controls, patients with hyperprolactinemia generally had worse quality of life, anxiety, depression and certain personality traits. Patients receiving DAs had higher impulsivity scores than normoprolactinemic controls. Impulse control disorders (ICDs) were reported in both genders, with hypersexuality mostly in men. Multiple ICDs were sometimes reported in the same patient, usually reversible after DA discontinuation. In case reports, DA therapy was temporally associated with severe depression, manic episodes or psychosis, which improved after discontinuation and administration of psychiatric medications. Gender type of DA, dose and duration of therapy did not correlate with occurrence of psychiatric pathology. Conclusion Patients with hyperprolactinemia receiving DAs may develop changes in mood and behavior regardless of prior psychiatric history. Increased awareness for ICDs, depression, mania and other types of psychosis is needed by all physicians who prescribe DAs. Larger prospective controlled clinical studies are needed to delineate prevalence, risk stratification and management.

Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function.

The main active ingredient in cannabis, delta-9-tetrahydrocannabinol (THC), can acutely induce psychotic symptoms and impair episodic and working memory. Another major constituent, cannabidiol (CBD), may attenuate these effects. This study aimed to determine the effects of THC and CBD, both alone and in combination on psychotic symptoms and memory function. A randomised, double-blind crossover design compared the effects of (i) placebo, (ii) THC 8 mg, (iii) CBD 16 mg and (iv) THC 8 mg + CBD 16 mg administered by inhalation through a vaporiser. Using an experimental medicine approach to predict treatment sensitivity, we selected 48 cannabis users from the community on the basis of (1) schizotypal personality questionnaire scores (low, high) and (2) frequency of cannabis use (light, heavy). The Brief Psychiatric Rating Scale (BPRS), Psychotomimetic States Inventory (PSI), immediate and delayed prose recall (episodic memory), 1- and 2-back (working memory) were assessed on each day. Results indicated that THC increased overall scores on the PSI, negative symptoms on BPRS, and robustly impaired episodic and working memory. Co-administration of CBD did not attenuate these effects. CBD alone reduced PSI scores in light users only. At a ratio of 2:1, CBD does not attenuate the acute psychotic and memory impairing effects of vaporised THC. Frequent cannabis users may show a blunted anti- psychotic response to CBD, which is of concern due to the high rates of cannabis use disorders in patients with schizophrenia.