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.

Proportion of Antipsychotics with CYP2D6 Pharmacogenetic (PGx) Associations Prescribed in an Early Intervention in Psychosis (EIP) Cohort: A Cross-Sectional Study.

BACKGROUND: Prescribing drugs for psychosis (antipsychotics) is challenging due to high rates of poor treatment outcomes, which are in part explained by an individual's genetics. Pharmacogenomic (PGx) testing can help clinicians tailor the choice or dose of psychosis drugs to an individual's genetics, particularly psychosis drugs with known variable response due to CYP2D6 gene variants ('CYP2D6-PGx antipsychotics'). AIMS: This study aims to investigate differences between demographic groups prescribed 'CYP2D6-PGx antipsychotics' and estimate the proportion of patients eligible for PGx testing based on current pharmacogenomics guidance. METHODS: A cross-sectional study took place extracting data from 243 patients' medical records to explore psychosis drug prescribing, including drug transitions. Demographic data such as age, sex, ethnicity, and clinical sub-team were collected and summarised. Descriptive statistics explored the proportion of 'CYP2D6-PGx antipsychotic' prescribing and the nature of transitions. We used logistic regression analysis to investigate associations between demographic variables and prescription of 'CYP2D6-PGx antipsychotic' versus 'non-CYP2D6-PGx antipsychotic'. RESULTS: Two-thirds (164) of patients had been prescribed a 'CYP2D6-PGx antipsychotic' (aripiprazole, risperidone, haloperidol or zuclopenthixol). Over a fifth (23%) of patients would have met the suggested criteria for PGx testing, following two psychosis drug trials. There were no statistically significant differences between age, sex, or ethnicity in the likelihood of being prescribed a 'CYP2D6-PGx antipsychotic'. CONCLUSIONS: This study demonstrated high rates of prescribing 'CYP2D6-PGx-antipsychotics' in an EIP cohort, providing a rationale for further exploration of how PGx testing can be implemented in EIP services to personalise the prescribing of drugs for psychosis.

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.

Una visión clínica de los síntomas psicóticos inducidos por sustancias en una sala de venopunción supervisada: Una década de experiencia / A clinical view of substance-induced psychotic symptoms in a supervised venipuncture room: A decade of experience

Introducción. Las salas de venopunción supervisadas (MSIR) son centros extremadamente importantes para las personas que usan drogas intravenosas (PWID), ya que las MSIR brindan un lugar sanitariamente seguro para el consumo de sustancias psicoativas ilícitas, teniendo un impacto importante en las tasas de sobredosis y las infecciones virales transmitidas por vía sanguínea. Métodos. Descripción de los síntomas psicóticos inducidos observados en una MSIR y su relación con la sustancia utilizada. El análisis se realizó con datos recopilados entre el 01/01/2009 y el 31/08/2021. Resultados. Se registraron 3731 autoinyecciones (68,7% heroína, 29,1% cocaína, 2,1% speedball y 0,2% otra sustancia) durante el período estudiado. Los síntomas psicóticos solo se observaron en el 7,1% del total de autoinyecciones. Sin embargo, se detectaron grandes diferencias entre las sustancias: el 23,2% de los consumos de cocaína estuvieron relacionados con síntomas psicóticos, el 20,8% de las inyecciones de speedball presentaron síntomas psicóticos y solo el 0,3% de las venopunciones de heroína se relacionaron con síntomas psicóticos (X2 =604.99; p<0.001). Además, algunas variables señalan que los síntomas psicóticos inducidos por sustancias pueden estar asociados con una mayor gravedad clínica. Conclusiones. Los sujetos con consumo de cocaína o speedball que acuden a MSIR pueden presentar síntomas psicóticos inducidos por sustancias, siendo esto un criterio de mayor gravedad clínica. Por lo tanto, los protocolos de las MSIR deben analizarse y adaptarse en función de la sustancia utilizada y la inducción de síntomas psicóticos. Además, se necesita más investigación en esta área. (AU)

Introduction. Medically supervised injecting rooms (MSIRs) are extremely important facilities for people who inject drugs (PWID) as MSIRs provide a safe place for the consumption of street-sourced drugs, impacting overdose rates and viral transmitted infections. Methods. The current paper describes more than 10 years of our MSIR experience regarding psychotic symptoms and their relationship with the substance used. The analysis was performed using data collected between 01/01/2009 and 08/31/2021. Results. 3731 self-injections (68.7% heroin, 29.1% cocaine, 2.1% speedball, and 0.2% other substance) were recorded during the studied period. Psychotic symptoms were only observed in 7.1% of the total self-injections. However, large differences were detected among substances: 23.2% of cocaine consumptions were related to psychotic symptoms, 20.8% of speedball injections presented psychotic symptoms, and only 0.3% of heroin consumptions had psychotic symptoms (X2=604.99; p<0.001). Also, some other variables highlight that psychotic symptoms induced by substances may be associated with higher clinical severity. Conclusions. subjects with cocaine or speedballuse who attend MSIRs may present substance-induced psychotic symptoms, having higher clinical severity. Thus, MSIRs’ protocols should be analyzed and adapted in terms of the substance used and the induction of psychotic symptoms. Moreover, further research is necessary on this critical issue. (AU)

How does a family history of psychosis influence the risk of methamphetamine-related psychotic symptoms: Evidence from longitudinal panel data.

AIMS: To determine whether the risk of psychotic symptoms during weeks of methamphetamine use was dependent on, increased by, or independent of having a family history of psychosis. DESIGN: Secondary analysis of 13 contiguous 1-week periods of data (1370 weeks). A risk modification framework was used to test each scenario. SETTING: Geelong, Wollongong and Melbourne, Australia. PARTICIPANTS: Participants in a randomized controlled trial of treatment for methamphetamine dependence (n = 148) who did not have a primary psychotic disorder on enrolment. MEASUREMENTS: Psychotic symptoms in the previous week were defined as a score of 3+ on any of the Brief Psychiatric Rating Scale items of hallucinations, unusual thought content or suspiciousness. Any (vs no) methamphetamine use in the previous week was assessed using the Timeline Followback method. Self-reported family history of psychosis was assessed using the Diagnostic Interview for Psychosis. FINDINGS: The risk of psychotic symptoms in the past week was independently associated with methamphetamine use in that week (relative risk [RR] = 2.3, 95% CI = 1.3-4.3) and with having a family history of psychosis (RR = 2.4, 95% CI = 0.9-7.0); the joint risk among participants with a family history of psychosis during weeks when they were using methamphetamine was large (RR = 4.0, 95% CI = 2.0-7.9). There was no significant interaction between a family history of psychosis and methamphetamine use in predicting psychotic symptoms (interaction RR = 0.7 95% CI = 0.3-1.8), but there was a small non-significant excess risk due to the interaction (0.20 95% CI = -1.63 to 2.03). CONCLUSIONS: Among people dependent on methamphetamine, the relative risk of psychotic symptoms during weeks of methamphetamine use does not appear to be dependent on, or increased by, having a family history of psychosis. However, a family history of psychosis does appear to be an independent risk factor that contributes to the absolute risk of psychotic symptoms in this population.

Psychopathology and Pattern of Remission of Cannabis-Induced Psychotic Disorder.

Objective: To analyze the psychopathology and pattern of remission in cannabis-induced psychotic disorder with treatment.Methods: This was a prospective cohort study of a group of patients admitted with new-onset psychosis, cannabis use, and no evidence of other drug abuse from January 1 to June 31, 2019, to the psychiatry inpatient department of a multispecialty tertiary care hospital in Kerala, India. Patients were evaluated at admission and after 1 week in the hospital and 1 month after discharge using the Structured Clinical Interview for the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Severity of illness scale.Results: Fifty-six male subjects were recruited for the study. The mean age of the subjects was 22.2 years, and the majority were active smokers of nicotine and cannabis. Total duration of abuse and family history of substance use in first-degree relatives correlated with severity of psychosis. Hostility, excitement, and grandiosity were the predominant positive symptoms, and these symptoms showed a steady reduction toward the end of the study. The most frequent negative symptoms were emotional withdrawal, passive or apathetic social withdrawal, and difficulty in abstract thinking, and these symptoms also showed significant improvement (P < .001 for all). For symptoms such as somatic concern and guilt feelings, significant treatment response was noted only in the initial week (P < .001).Conclusions: Cannabis-induced psychosis in the Indian setting presents with predominant positive symptoms and minimal affective symptoms. The steady improvement noted with complete cessation of cannabis indicates a possible contributory role for cannabis in precipitating psychosis.

Differences between substance-induced psychotic disorders and non-substance-induced psychotic disorders and diagnostic stability. / Diferencias y estabilidad diagnóstica entre trastornos psicóticos inducidos por sustancias y trastornos psicóticos no inducidos.

Several hypotheses have been proposed to explain the comorbidity between psychotic disorders and substance use, one of them being the capacity of some to induce psychotic symptoms, although the transition from psychotic episodes induced by substances to schizophrenia has been less studied. In this study, differential variables between patients with induced and non-induced psychosis are determined, and the evolution and change of diagnosis of those induced to schizophrenia in the follow-up is analyzed. This is an observational case-control study with 238 patients admitted to the acute care unit for psychotic episodes between December 2003 and September 2011. The group of non-substance-induced psychotic disorders (NSIPD) included 127 patients, with 111 in the substance-induced (SIPD) group, according to the International Classification of Diseases. Sociodemographic and clinical characteristics, personal and family history, substance use, diagnostic stability and progression were compared. The NSIPD group showed higher scores in severity and in negative symptoms and more family history of psychosis. The SIPD group presented more personal history of personality disorder and family history of addictions and more positive symptoms At 6 years of follow-up, 40.9% of ISDP changed to a diagnosis of schizophrenia, presenting more family history of psychotic disorders and worse progression with more visits to the emergency department and readmissions, than subjects who maintained diagnostic stability. Therefore, special attention should be paid to this group of patients because of the potential severity and the increased risk of developing a chronic psychotic disorder.

Se han propuesto distintas hipótesis para explicar la comorbilidad entre trastornos psicóticos y por consumo de sustancias, siendo una de ellas la capacidad de algunas de inducir cuadros psicóticos, aunque la transición de episodios psicóticos inducidos por sustancias a esquizofrenia ha sido menos estudiada. En este trabajo se determinan variables diferenciales entre individuos con psicosis inducidas y no inducidas, y se analiza la evolución y el cambio de diagnóstico de las inducidas a esquizofrenia en el seguimiento. Es un estudio observacional de casos y controles con 238 pacientes ingresados en la unidad de agudos de un Hospital General de Madrid (España) por episodios psicóticos entre diciembre de 2003 y septiembre de 2011. Se incluyeron 127 en el grupo de trastornos psicóticos no inducidos por sustancias (TPNIS) y 111 en el de inducidos por sustancias (TPIS), según la Clasificación Internacional de Enfermedades. Se compararon características sociodemográficas, clínicas, antecedentes personales y familiares, de consumo de sustancias, estabilidad diagnóstica y evolución. El grupo de TPNIS presentó mayores puntuaciones en gravedad y sintomatología negativa mientras que el de TPIS tuvo más antecedentes personales de trastorno de personalidad y familiares de adicciones, y más sintomatología positiva. A los seis años un 40,9% de TPIS cambió a diagnóstico de esquizofrenia, presentando más antecedentes familiares de trastornos psicóticos y de adicciones, y una peor evolución con más visitas a urgencias y reingresos que los sujetos con estabilidad diagnóstica. Por tanto, habrá que prestar especial atención a este grupo de sujetos por su potencial gravedad y por el mayor riesgo de desarrollar un trastorno psicótico crónico.

First episode psychosis with and without the use of cannabis and synthetic cannabinoids: Psychopathology, global functioning and suicidal ideation and antipsychotic effectiveness.

BACKGROUND: Natural Cannabis (NC) and Synthetic Cannabinoids (SCs) use can increase the risk of developing psychotic disorders and exacerbate their course. AIMS: To examine the differences between psychoses not associated with cannabis use and those associated with NC and SCs use, evaluating psychotic symptoms, global functioning, dissociative symptoms and suicidal ideation. METHODS: The sample of 61 patients with First Episode Psychosis (FEP) was divided into 3 groups: non-Cannabis users (non-users, N = 20); NC users (THC-users, N = 21); SCs users (SPICE-users, N = 20). Each group was assessed at FEP and after 3 and 9 months through specific psychopathological scales. RESULTS: THC-users, and even more SPICE-users, displayed much more severe positive symptoms than non-users. Negative symptoms were higher among non-users. After 9 months the non-users had recovered significantly better than SPICE-users in their global functioning. Dissociative symptoms were significantly greater in substance users. Finally, suicidal ideation was higher in SPICE-users than in both THC-users and non-users. DISCUSSION: The psychoses induced by NC and SCs showed different symptomatic pictures and outcomes from each other and when compared to the psychoses not associated with the use of substances; such knowledge could be relevant in identifying a specific drug treatment.

Higher lymphocyte count associated with larger hippocampal volume and fewer depressive symptoms in drug-na ïve first-episode psychosis.

Circulating white blood cells (leucocytes), which form the peripheral immune system, are crucial in inflammatory processes but their role in brain structural change in schizophrenia has been scarcely studied. With this study we want to determine how and which type of white blood cells are associated with hippocampal volume (as a key structure in schi- zophrenia etiopathology) in first episode psychosis (FEP) patients. Moreover, to determine the association between white blood cells and clinical symptomatology, including positive and negative symptoms, cognition and depression. For this purpose fifty drug-naïve FEP were included in this study. All patients underwent an assessment at baseline and at 1 year follow-up, including sociodemographic and clinical variables (substance use, DUP, PANSS, GAF and CDSS). Fasting blood samples were obtained before administering any medication at baseline. Structural T1 MRI was performed at baseline and brain volumes were quantified. In the present study, higher lymphocyte count was associated with larger right hippocampal volume at baseline in FEP drug-naive patients. Higher lymphocyte count was associated with lower depressive symptomatology measured with CDSS and Marder depressive factor from PANSS at baseline and 1-year follow -up. These results suggest that lymphocytes may have a protective effect in hippocampal volume at baseli- ne in antipsychotic naïve FEP and also, are associated with a better depressive course over follow up. These results open the door to identify new biomarkers and therapeutic targets for patients with schizophrenia.