Serotonin syndrome caused by escitalopram in Parkinson's disease psychosis: a case report.

BACKGROUND: Serotonin syndrome and Parkinson's disease (PD) are two diseases whose symptoms partially overlap; this poses challenges in distinguishing them in clinical practice. Early manifestations such as tremor, akathisia, diaphoresis, hypertonia and hyperreflexia are common in mild-to-moderate serotonin syndrome and can also occur in PD. Without prompt recognition and treatment, serotonin syndrome can rapidly progress, potentially leading to severe complications such as multiple organ failure within hours. Given their disparate treatment strategies, accurate clinical distinction is crucial for effective treatment. This case study explores a patient with serotonin syndrome triggered by escitalopram in the context of PD psychosis (PDP), providing insights into diagnosis and treatment planning. CASE PRESENTATION: A 75-year-old Asian woman with a one-year history of PD, a two-month history of PDP, and a six-year history of depression presented with symptoms including hyperreflexia, tremor, hypertonia, impaired level of consciousness, and inappropriate behavior following a recent one-month adjustment in medication. Initially suspected of being drug-induced parkinsonism or worsening PD, therapeutic drug monitoring revealed warning levels of escitalopram. Subsequent diagnoses confirmed serotonin syndrome. This syndrome may result from increased cortical serotonin activity at the serotonin2A receptor due to dopamine and serotonin imbalances in PDP, compounded by increased dopamine-mediated serotonin release. Additionally, being an intermediate metabolizer of cytochrome P450 enzyme 2C19, the patient experienced excessive escitalopram accumulation, exacerbating her condition. CONCLUSIONS: This case underscores the critical need to differentiate between symptoms of serotonin syndrome and PD, particularly in manifestations like tremor and hypertonia. Careful consideration of receptor profiles in patients with PDP is essential when selecting antidepressants to mitigate the risk of serotonin syndrome.

The Role of Cannabis in the Development of Psychosis. / Esrarin Psikoz Gelisimindeki Rolü.

Cannabis is known to cause psychotic disorders, and the increasing use of cannabis constitutes an important health problem. Growing evidence that cannabis causes the development of psychosis has led to an increase in the number of studies in this field. This review aims to clarify the role of cannabis use in the development of psychosis, discuss the current literature about the underlying neurobiological mechanisms. For this purpose PubMed was searched for the keywords "cannabis use, psychosis, schizophrenia, endocannabinoid system, pathophysiology, neurobiology"; the articles published in the last 10 years were reviewed. Epidemiological studies showed that cannabis use starting at an earlier age is associated with an increased risk of psychosis, this risk is more pronounced in people with genetic predisposition and increases with heavy and high potency cannabis use. Studies showed that the endocannabinoid system, which plays a role in nervous system development and functions as a homeostatic regulator in physiological processes, is affected by cannabis use during critical periods of development like adolescence; cannabis use affects physiological processes such as synaptic pruning due to the effects of this system on neurotransmitters like glutamate and dopamine leading to long-term behavioral and psychological consequences. Additionally, evidence that dysfunctions in the endocannabinoid system play a role in the etiology of schizophrenia suggests that cannabis affects the disease process by worsening existing dysfunctions in this system. Understanding the relationship between cannabis use and the development of psychosis and underlying neurobiological mechanisms will help to identify new treatment targets, and develop appropriate preventive approaches. Keywords: Cannabis Abuse, Psychotic Disorders, Schizophrenia, Endocannabinoids, Neurobiology.

Ketamine-dependent patients with persistent psychosis have higher neurofilament light chain levels than patients with schizophrenia.

OBJECTIVES: Ketamine can induce persisting psychosis in a subset of individuals who use it chronically and heavily. Previously, we found that the psychopathology and cognitive impairments in patients with ketamine dependence (KD) exhibiting persistent psychosis (KPP) bear resemblances with schizophrenia, albeit with less severity in those with no persistent psychosis (KNP). Furthermore, we also showed that patients with KD had higher blood levels of neurofilament light chain (NFL), a biomarker for neuroaxonal injury, compared to healthy controls. In this study, we aimed to investigate the differences in NFL levels between patients with KPP and KNP while comparing the levels of individuals with schizophrenia and healthy controls. METHODS: We enrolled 64 treatment-seeking ketamine-dependent patients (53 with KNP and 11 with KPP), 37 medication-free patients with schizophrenia, and 80 healthy controls. Blood NFL levels were measured by single molecule array immunoassay. RESULTS: NFL levels were highest in the KPP subgroup, followed by the KNP subgroup, and then the schizophrenia and control groups (mean ± SD: 24.5 ± 24.7, 12.9 ± 10.9, 9.2 ± 12.2, and 6.2 ± 2.2 pg/mL, respectively), with no significant difference observed between the schizophrenia and control groups. CONCLUSIONS: We found that KD is associated with higher NFL levels compared to schizophrenia, with the KPP subgroup showing the most consistent alterations. The observation of accentuated neuroaxonal pathology in individuals with KPP implies that this clinical manifestation is associated with a specific neurobiological phenotype, despite prior evidence suggesting syndromal similarity between schizophrenia and KPP.

Drug-induced psychosis following use of Ayahuasca: a presentation to forensic psychiatric services.

Ayahuasca is a plant-based psychoactive decoction, traditionally used by indigenous Amazonian peoples, which commonly contains the hallucinogen N,N-dimethyltryptamine (DMT). There is now growing interest across the Western world in psychedelics including Ayahuasca.This case describes a previously well male with no risk factors for adverse psychiatric outcomes or forensic history. Following controlled Ayahuasca use, he developed an enduring psychotic episode, during which he significantly assaulted a relative and was admitted to a forensic psychiatric unit. He was treated with the antipsychotic aripiprazole, and his psychotic symptoms abated. 18 months following his admission, recovery has been sustained.Previous case reports have described psychosis following Ayahuasca ingestion, but typically of short duration in patients with a personal or family history of psychiatric illness, or in those taking other substances. With the growing use of Ayahuasca, it is important to highlight that adverse effects may include more prolonged psychotic symptoms and the risk of psychotically mediated violence.

The Resurgence of Exogenous Psychosis: A Phenomenological Examination of Substance-Induced Psychopathology.

ABSTRACT: The psychopathological manifestations associated with substance use, including induced psychotic experiences, are increasingly relevant but not well-understood within the medical community. Novel psychoactive substances and potentiated old compounds like cannabis and cocaine have emerged as a global concern, especially among adolescents and young adults. Transition rates from substance-induced psychosis (SIP) to persistent psychosis are significant, particularly in cases of cannabis-induced psychosis. Scientific inquiry into induced psychotic phenomena has revealed differences between SIP and primary psychotic disorders, highlighting the risk factors associated with each. The concept of exogenous psychosis, including its toxic variant known as lysergic psychoma, provides valuable insights into the role of external factors in psychosis development. A phenomenological approach characterizes this disruption in perception as a shift in temporal and spatial dimensions, leading to auditory and visual hallucinations. The "twilight state" of consciousness plays a crucial role in the transition from substance use to psychosis, with implications for spatiality, intersubjectivity, and temporality. This complex path to psychosis challenges traditional diagnostic models and underscores the need for a more nuanced understanding of substance-induced psychopathological experiences.

The General Neurocognitive Decline in Patients with Methamphetamine Use and Transient Methamphetamine-induced Psychosis is Primarily Determined by Oxidative and AGE-RAGE Stress.

BACKGROUND: Chronic Methamphetamine (MA) usage is linked to oxidative and AGE (advanced glycation end products) - RAGE (receptors for AGEs) stress, changes in magnesium, calcium, and copper, increased psychotic symptoms, and neurocognitive deficits. Nevertheless, it is still unclear whether these biological pathways mediate the latter impairments. OBJECTIVE: This study aimed to investigate the relationships between neurocognition, the aforementioned biomarkers, and psychotic symptoms. METHODS: We recruited 67 participants, namely 40 patients diagnosed with MA-substance use and 27 healthy controls, and assessed the Brief Assessment of Cognition in Schizophrenia (BACS), symptoms of psychosis, excitation, and formal thought disorders, oxidative toxicity (computed as the sum of myeloperoxidase (MPO), oxidized high-density lipoprotein (HDL), oxidized low-DL, and malondialdehyde), antioxidant defenses (catalase, glutathione peroxidase, total antioxidant capacity, zinc, and HDL), and increased AGEs and RAGEs. RESULTS: We were able to extract one validated latent vector from the Mini-Mental State Examination score and the BACS test results (including executive functions, verbal fluency, and attention), labeled general cognitive decline (G-CoDe). We found that 76.1% of the variance in the G-CoDe was explained by increased oxidative toxicity, lowered antioxidant defenses, number of psychotic episodes, and MA dose. In patients with MA use, MPO was significantly associated with the GCoDe. CONCLUSION: The use of MA induced mild cognitive impairments through MA-induced activation of detrimental outcome pathways, including oxidative and AGE-RAGE stress, and suppression of protective antioxidant pathways. Increased MPO, oxidative, and AGE-RAGE stress are new drug targets to prevent neurocognitive deficits and psychosis due to MA use.

Psychosis in cocaine intoxication.

Background: Cocaine overdose is a condition in which an increase in blood pressure, heart rate and depth of breath is observed. Cocaine consumption also causes a wide and well-known neuropsychiatric symptomatology that is characterized by incomprehensible behavior, confused and disordered thoughts, and paranoia. Cocaine addiction is a worldwide public health problem, which has somatic, psychological, psychiatric, socio-economic, and judicial complications. Case series: This work shows three cases in which cocaine poisoning and overdose caused a psychotic and extremely violent behavior in the hours leading up to the death of the subjects. Conclusion: The aim of this brief case series is to suggest some diagnostic criteria for the correct definition of this psychosis in order to make an early diagnosis crucial to prevent deaths related to it.

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.

Psychotomimetic compensation versus sensitization.

It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a short-term stressor or drug-induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic-like experiences over time. Theoretical and practical implications of this model are discussed.

Evaluation of methamphetamine assist packs: As-needed antipsychotics for self-management of methamphetamine-associated psychiatric toxicity.

BACKGROUND: Methamphetamine frequently causes substance-induced psychosis and related symptoms. There are currently no interventions to prevent or assist in self-management of these symptoms. METHODS: We evaluated a program providing "Methamphetamine Assist Packs" to patients who were seen in a psychiatric emergency services program for methamphetamine-induced psychosis. Methamphetamine Assist Packs included a small number of tablets of an antipsychotic medication (olanzapine), administration instructions, and referral information. We reviewed medical charts of patients who received Methamphetamine Assist Packs from January 2022 through May 2023 for sociodemographic and emergency visit characteristics. We assessed the changes between the number of psychiatric emergency visits before and after Methamphetamine Assist Pack receipt at two, six, and 12 months using generalized estimating equations. RESULTS: Ninety-two patients received a Methamphetamine Assist Pack, with a mean age of 40 years; 79 % were male and 49 % Black/African American; 77 % experienced housing instability or homelessness. The most common symptoms were suicidal ideation (54 %), paranoia or delusions (45 %), and hallucinations (40 %); 55 % were on involuntary psychiatric hold, 38 % required medications for agitation, and 18 % required seclusion or physical restraints. The rate of psychiatric emergency visits after Methamphetamine Assist Pack receipt was 0.68 and 0.87 times the rate prior to receipt at two and six months, respectively (p < 0.001). There was no difference at 12 months. CONCLUSIONS: Methamphetamine Assist Packs were associated with fewer psychiatric emergency visits for six months after receipt, and represent a promising intervention to address acute psychiatric toxicity from methamphetamine in need of further research.

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.

The Loss of Spatiality and Temporality in Twilight Consciousness: The Emergence of Exogenous Psychosis Induced by Novel Psychoactive Substances.

BACKGROUND: The state of twilight consciousness is marked by a focused narrowing of awareness, maintaining vigilance and attention while simultaneously experiencing perceptual shifts in the surrounding environment. It is crucial to recognize that this twilight state represents not just a contraction but also an expansion of conscious experience. SUMMARY: Substances of abuse, particularly new psychoactive substances, play a significant role in inducing this twilight state. They achieve this by deconstructing essential components of consciousness, such as the perception of time and space. KEY MESSAGE: This paper aimed to explore the phenomenon of the twilight state of consciousness and shed light on how new psychoactive substances can alter the perception of time and space during this twilight phase, potentially triggering exogenous psychosis. This comprehensive inquiry employs a phenomenological approach to the study of consciousness, recognizing it as the primary tool for ascribing significance to this intricate yet often overlooked aspect of psychopathology.

A systematic review and meta-analysis of synthetic cathinone use and psychosis.

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.

Positive and negative symptoms in methamphetamine-induced psychosis compared to schizophrenia: A systematic review and meta-analysis.

BACKGROUND: The clinical profiles of methamphetamine-induced psychosis (MIP) and schizophrenia are largely overlapping making differentiation challenging. In this systematic review and meta-analysis, we aim to compare the positive and negative symptoms of MIP and schizophrenia to better understand the differences between them. STUDY DESIGN: In accordance with our pre-registered protocol (CRD42021286619), we conducted a search of English-language studies up to December 16th, 2022, in PubMed, EMBASE, and PsycINFO, including stable outpatients with MIP and schizophrenia. We used the Newcastle-Ottawa Scale to measure the quality of cross-sectional, case-control, and cohort studies. STUDY RESULTS: Of the 2052 articles retrieved, we included 12 studies (6 cross-sectional, 3 case-control, and 2 cohort studies) in our meta-analysis, involving 624 individuals with MIP and 524 individuals with schizophrenia. Our analysis found no significant difference in positive symptoms between the two groups (SMD, -0.01; 95%CI, -0.13 to +0.11; p = 1). However, individuals with MIP showed significantly less negative symptoms compared to those with schizophrenia (SMD, -0.35; 95CI%, -0.54 to -0.16; p = 0.01; I2 = 54 %). Our sensitivity analysis, which included only studies with a low risk of bias, did not change the results. However, our meta-analysis is limited by its cross-sectional approach, which limits the interpretation of causal associations. Furthermore, differences in population, inclusion criteria, methodology, and drug exposure impact our findings. CONCLUSIONS: Negative symptoms are less prominent in individuals with MIP. While both groups do not differ regarding positive symptoms, raises the possibility of shared and partly different underlying neurobiological mechanisms related to MIP and schizophrenia.

New-Onset Prolonged Psychosis Following Synthetic Cannabinoid Use in an Older Patient: A Case Report.

Synthetic cannabinoids (SCs), a class of new psychoactive substances (NPS) commonly known as "spice," has rapidly gained popularity and become the most ubiquitous NPS on the illegitimate drug market. SCs, unlike natural cannabis (NC), are not controlled by international drug conventions, posing a significant risk to public health. These substances are easily accessible, relatively inexpensive, and challenging to detect in routine drug screenings. The existing literature provides strong evidence of an association between NC use and psychosis, but there is significantly less data on SC psychosis. We present a clinical case report of a 51-year-old African American female with no known psychiatric history who was admitted to the inpatient psychiatric unit after reported paranoia and altered mental status for the preceding six days. During hospitalization, she exhibited disorganization, persecutory delusions, extreme agitation, and bizarre behaviors that included the concealment of a set of stolen keys in her vagina, necessitating an ethics consult. After consideration of differentials, the patient was diagnosed with substance-induced psychotic disorder secondary to SC. The patient was stabilized on 3 mg Risperidone at bedtime. After 16-day hospitalization, she reached her baseline and later revealed that she had recently smoked SC for the first time. The primary goal of this case is to highlight the sequelae of SC-associated psychosis. A SC-associated psychosis could drastically vary from NC and is often undetectable on a typical UDS, which may result in a lifelong primary psychotic disorder misdiagnosis.