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.

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.

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.

Methamphetamine use and psychotic symptoms: findings from a New Zealand longitudinal birth cohort.

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.

Characteristics of Amphetamine Psychosis with Respect to the Length of Drug Exposure.

BACKGROUND: Over the past decade, the number of individuals requiring medical care for amphetamine-related psychosis has increased. OBJECTIVE: This study aims to examine the psychological characteristics of amphetamine psychosis in drug-addicted patients depending on the length of drug exposure and compared to patients diagnosed with paranoid schizophrenia. METHODS: The study was carried out in psychiatric clinic No. 1 in Kyiv (Ukraine) in 2019, involving 107 patients. Of all the participants, 50 were included in Group 1 (methamphetamine psychosis) and 57 - in Group 2 (paranoid schizophrenia). All patients were treated with medication to relieve exacerbating symptoms. They underwent extensive testing to determine the impairment severity of cognitive function, attention, and task performance during remission. RESULTS: In Group 1, the timing of onset for paranoid symptoms depends on the length of amphetamine exposure (Spearman correlation coefficient = 0.89). The efficacy and dynamics of drug treatment in Group 2 were similar to patients in Group 1. However, the effect of reduction in Group 2 was achieved only in 4 months. Delusions, emotional disturbances, hallucinations in patients of Group 1 occurred 2.3 times more frequently than in Group 2 (p ≤ 0.05). The patients of Group 1 are characterized by the presence of disorders related to the affective and behavioral components. CONCLUSION: All reported exacerbations are related to amphetamine use. Patients in Group 1 learned a smaller number of words compared to those in Group 2. Besides, a large number of errors and difficulties with shifting focus were recorded.

Annual incidence of substance-induced psychoses in Scandinavia from 2000 to 2016.

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.

Sleep Deprivation & Amphetamine Induced Psychosis.

Objectives: To explore the relationship between sleep deprivation and amphetamine-induced psychosis. Methods: The patient group included 78 patients with a diagnosis of amphetamine (Captagon)-induced psychosis. The control group included 49 patients with no current or past history of amphetamine (Captagon)-induced psychosis. All study subjects underwent the following: a demographic sheet, a structured clinical interview for SM-IV (SCID 1), a drug use questionnaire, a questionnaire to explore any relationship between sleep deprivation and Captagon-induced psychosis, routine medical investigation, and urine screening for detection of drugs. Results: The patient group showed significantly higher both regular and maximum daily doses of Captagon. Patients showed more periods of sleep deprivation with the use of Captagon in comparison to controls, especially with the increase of the Captagon dose. Patients believed that the occurrence and termination of sleep deprivation were the cause of the start and end of psychotic experiences (more so than the increase and decrease or stoppage of Captagon doses). Conclusion: sleep deprivation plays an essential role in the development of psychotic symptoms in patients who are using Captagon.

Cannabis - miracle medicine or psychosis-inducing drug? / Cannabis ­ mirakelmedisin eller psykosefremkallende rusmiddel?

Throughout history, cannabis has been suggested as a treatment for numerous diseases. Despite being in use for over 5000 years, cannabis is still a hot topic of debate and the subject of discussion among politicians and the medical community.