'I am proud of how I handled it'. Exploring the impact of the COVID-19 pandemic and related restrictions on well-being of adults with severe mental illness using qualitative methods.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic and related restrictions globally impacted mental health, particularly for those with pre-existing severe mental illness (SMI). This qualitative study examined how adults with SMI perceived the effects of the COVID-19 pandemic and related restrictions in the Netherlands, focusing on their personal recovery, well-being and daily life, including an exploration of factors influencing these effects. METHODS: Semi-structured interviews were conducted, audio-recorded and transcribed verbatim. Reflexive thematic analysis was applied. Purposive sampling was used to ensure diversity of individuals with SMI (i.e., age, gender, diagnosis, cultural background and mental healthcare institution). RESULTS: Twenty participants (median age: 45 years [SD: 12, 8]; 11 females) were interviewed between May and July 2023. Findings revealed a wide range of experiences: while some individuals reported a negative impact on their existing psychiatric symptoms, others described adaptability, resilience and even positive effects of COVID-19 restrictions on their mental health and well-being. Factors influencing the heterogeneic perceptions of the COVID-19 pandemic and related restrictions include the availability of trusted social relationships and enduring interactions with health professionals. CONCLUSION: Personalised support, both socially and professionally, is crucial for addressing fears, building resilience, reducing isolation and encouraging positive coping strategies for individuals with SMI during external crises. In this project, a participatory research approach that integrated the lived experience perspective helped uncover the unique perceptions of people with SMI with regard to the pandemic and related restrictions. PATIENT OR PUBLIC CONTRIBUTION: The study used a participatory action research approach, with experts-by-experience involved in every stage of the project as part of the research team. This included engagement with the funding application process, recruitment strategies for interviews, developing the interview guide, piloting the interview, interpreting findings, and knowledge dissemination activities.

Practice variation in opioid prescribing for non-cancer pain in Dutch primary care: A retrospective database study.

BACKGROUND: Prescription opioid use has increased steadily in many Western countries over the past two decades, most notably in the US, Canada, and most European countries, including the Netherlands. Especially the increasing use of prescription opioids for chronic non-cancer pain has raised concerns. Most opioids in the Netherlands are prescribed in general practices. However, little is known about variation in opioid prescribing between general practices. To better understand this, we investigated practice variation in opioid prescribing for non-cancer pain between Dutch general practices. METHODS: Data from 2017-2019 of approximately 10% of all Dutch general practices was used. Each year included approximately 1000000 patients distributed over approximately 380 practices. The primary outcome was the proportion of patients with chronic (>90 days) high-dose (≥90 oral morphine equivalents) opioid prescriptions. The secondary outcome was the proportion of patients with chronic (<90 oral morphine equivalents) opioid prescriptions. Practice variation was expressed as the ratio of the 95th/5th percentiles and the ratio of mean top 10/bottom 10. Funnel plots were used to identify outliers. Potential factors associated with unwarranted variation were investigated by comparing outliers on practice size, patient neighbourhood socioeconomic status, and urbanicity. RESULTS: Results were similar across all years. The magnitude of variation for chronic high-dose opioid prescriptions in 2019 was 7.51-fold (95%/5% ratio), and 15.1-fold (top 10/bottom 10 ratio). The percentage of outliers in the funnel plots varied between 13.8% and 21.7%. Practices with high chronic high-dose opioid prescription proportions were larger, and had more patients from lower income and densely populated areas. CONCLUSIONS: There might be unwarranted practice variation in chronic high-dose opioid prescriptions in primary care, pointing at possible inappropriate use of opioids. This appears to be related to socioeconomic status, urbanicity, and practice size. Further investigation of the factors driving practice variation can provide target points for quality improvement and reduce inappropriate care and unwarranted variation.

Unity in diversity: A systematic review on the GHB using population.

BACKGROUND: Over the past decades gamma-hydroxybutyrate (GHB) has emerged as a popular drug with high potential of (ab)use due to its euphoric and relaxing effects. An overview of different populations using GHB is urgently needed, since this would enable development of adequate prevention and treatment policies to diminish the risks associated with GHB use. We systematically reviewed literature on different GHB using populations, comparing demographic characteristics, GHB use patterns, psychosocial aspects and psychiatric comorbidity. METHODS: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using Rayyan software. Original studies published from January 1997 up to October 2019 on GHB use were included. Out of 80 full-text articles, 60 articles of 51 unique studies were included. Most studies included people using GHB 1) presenting at emergency departments (n = 22), 2) recruited from the general population (n = 11), or 3) presenting at addiction care (n = 8). RESULTS: Three main sub-populations of people using GHB are described in the literature: people using GHB recreationally without adverse effects; people using GHB recreationally with adverse effects, and people with dependence on GHB. These groups show considerable overlap in gender, age range, and comorbid substance use, as well as amount of GHB use per occasion. Differences are related to frequency and function of GHB use, the number of comas experienced, as well as work status, and psychiatric comorbidity. CONCLUSION: Policy interventions should aim at preventing the transition from recreational substance use to GHB use, as most users are experienced recreational substance users prior to starting GHB use. When people use GHB regularly, interventions should aim at reducing the level of GHB use and preventing GHB use-related harm. Longitudinal studies and population-based probability sampling are required for more insight in the dynamics of GHB use in different sub-populations, and the transition from one group to the other, ultimately leading to dependence on GHB.

Perinatal exposure of rats to the HIV drug efavirenz affects medial prefrontal cortex cytoarchitecture.

Efavirenz (EFV) is used for antiretroviral treatment of HIV infection, and successfully inhibits viral replication and mother-to-child transmission of HIV during pregnancy and childbirth. Unfortunately, the drug induces neuropsychiatric symptoms such as anxiety and depressed mood and potentially affects cognitive performance. EFV acts on, among others, the serotonin transporter and serotonin receptors that are expressed in the developing brain. Yet, how perinatal EFV exposure affects brain cytoarchitecture remains unclear. Here, we exposed pregnant and lactating rats to EFV, and examined in the medial prefrontal cortex (mPFC) of their adult offspring the effects of the maternal EFV exposure on cortical architecture. We observed a significant decrease in the number of cells, mainly mature neurons, in the infra/prelimbic and cingulate cortices of adult offspring. Next, we found an altered cortical cytoarchitecture characterized by a significant reduction in deep- and superficial-layer cells. This was accompanied by a sharp increase in programmed cell death, as we identified a significantly higher number of cleaved Caspase-3-positive cells. Finally, the serotonergic and dopaminergic innervation of the mPFC subdomains was increased. Thus, the perinatal exposure to EFV provoked in the mPFC of adult offspring cell death, significant changes in cytoarchitecture, and disturbances in serotonergic and dopaminergic innervation. Our results are important in the light of EFV treatment of HIV-positive pregnant women, and its effect on brain development and cognitive behavior.

Tapering with Pharmaceutical GHB or Benzodiazepines for Detoxification in GHB-Dependent Patients: A Matched-Subject Observational Study of Treatment-as-Usual in Belgium and The Netherlands.

BACKGROUND: The gamma-hydroxybutyric acid (GHB) withdrawal syndrome often has a fulminant course, with a rapid onset and swift progression of severe complications. In clinical practice, two pharmacological regimens are commonly used to counteract withdrawal symptoms during GHB detoxification: tapering with benzodiazepines (BZDs) or tapering with pharmaceutical GHB. In Belgium, standard treatment is tapering with BZDs, while in the Netherlands, pharmaceutical GHB is the preferred treatment method. Though BZDs are cheaper and readily available, case studies suggest GHB tapering results in less severe withdrawal and fewer complications. OBJECTIVES: This study aimed to compare two treatments-as-usual in tapering methods on withdrawal, craving and adverse events during detoxification in GHB-dependent patients. METHODS: In this multicentre non-randomised indirect comparison of two treatments-as-usual, patients with GHB dependence received BZD tapering (Belgian sample: n = 42) or GHB tapering (Dutch sample: n = 42, matched historical sample). Withdrawal was assessed using the Subjective and Objective Withdrawal Scales, craving was assessed with a Visual Analogue Scale and adverse events were systematically recorded. Differences in withdrawal and craving were analysed using a linear mixed-model analysis, with 'days in admission' and 'detoxification method' as fixed factors. Differences in adverse events were analysed using a Chi-square analysis. RESULTS: Withdrawal decreased over time in both groups. Withdrawal severity was higher in patients receiving BZD tapering (subjective mean = 36.50, standard deviation = 21.08; objective mean = 8.05, standard deviation = 4.68) than in patients receiving pharmaceutical GHB tapering (subjective mean = 15.90; standard deviation = 13.83; objective mean = 3.72; standard deviation = 2.56). No differences in craving were found. Adverse events were more common in the BZD than the GHB group, especially delirium (20 vs 2.5%, respectively). CONCLUSIONS: These results support earlier work that BZD tapering might not always sufficiently dampen withdrawal in GHB-dependent patients. However, it needs to be taken into account that both treatments were assessed in separate countries. Based on the current findings, tapering with pharmaceutical GHB could be considered for patients with GHB dependence during detoxification, as it has potentially less severe withdrawal and fewer complications than BZD tapering.

Biochemical Effects on the Liver of 1 Month of Alcohol Abstinence in Moderate Alcohol Consumers.

SHORT SUMMARY: : In this study in healthy moderate alcohol consumers, we observe that one month of alcohol abstinence results in decreased gamma-glutamyl transferase levels, which return to baseline levels after resumption of alcohol consumption.

Ibogaine and addiction in the animal model, a systematic review and meta-analysis.

Ibogaine is a naturally occurring substance which has been increasingly used in the lay-scene to reduce craving and relapse in patients with substance use disorders (SUDs). Although human clinical trials on the safety and efficacy of ibogaine are lacking, animal studies do support the efficacy of ibogaine. In this systematic review and meta-analysis (MA), we summarise these animal findings, addressing three questions: (1) does ibogaine reduce addictive behaviour in animal models of SUDs?; (2) what are the toxic effects of ibogaine on motor functioning, cerebellum and heart rhythm?; (3) what are neuropharmacological working mechanisms of ibogaine treatment in animal models of SUDs? MA of 27 studies showed that ibogaine reduced drug self-administration, particularly during the first 24 h after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 h after supplementation, and cerebral cell loss even weeks after administration. Data on ibogaines effect on cardiac rhythm, as well as on its neuropharmacological working mechanisms are limited. Our results warrant further studies into the clinical efficacy of ibogaine in SUD patients in reducing craving and substance use, but close monitoring of the patients is recommended because of the possible toxic effects. In addition, more work is needed to unravel the neuropharmacological working mechanisms of ibogaine and to investigate its effects on heart rhythm.

Familial liability for metoprolol-induced psychosis.

OBJECTIVE: Beta-blockers are commonly used in the treatment of hypertension and cardiac arrhythmias. The incidence of neuropsychiatric side effects is generally low. This case report shows the potential familial liability of a metoprolol-induced psychosis. METHOD: We report a case of metoprolol-induced psychosis. Potential pharmocogenetic factors mediating this familial metoprolol-induced psychosis are discussed. RESULTS: A middle-aged man developed psychosis after starting metoprolol, which diminished after ceasing the medication. Two of his family members experienced similar symptoms after using metoprolol. All family members were genotyped as CYP2D6*4 allele carriers indicating reduced CYP2D6 enzyme activity. CONCLUSION: The case presented here suggests a potential familial liability for metoprolol- induced psychosis. Pharmacokinetic mechanisms are hypothesized to mediate this familial liability through genetic variation in the CYP2D6 genotype. A family history of psychotic symptoms after treatment with beta-blockers should be taken into account, when prescribing this beta-blocker.

Co-morbid anxiety disorders predict early relapse after inpatient alcohol treatment.

INTRODUCTION: Alcohol dependence and anxiety disorders often co-occur. Yet, the effect of co-morbid anxiety disorders on the alcohol relapse-risk after treatment is under debate. This study investigated the effect of co-morbid anxiety disorders on relapse rates in alcohol dependence. We hypothesized that co-morbid anxiety disorders would be particularly predictive for early relapse, but not late relapse. SUBJECTS AND METHODS: In a prospective design, male alcohol dependent patients (n=189) were recruited from an inpatient detoxification clinic. Psychiatric diagnoses and personality traits were assessed using the Mini International Neuropsychiatric Interview for psychiatric disorders and the Temperament and Character Inventory. The addiction severity index was used to assess addiction severity and follow-up. RESULTS: One year after detoxification, 81 patients (53%) relapsed and nine patients (7%) were deceased, due to alcohol related causes. Co-morbid anxiety disorder, marital status, addiction severity, in particular legal problems, and harm avoidance predicted relapse. Anxiety disorders specifically predicted early relapse. CONCLUSION: Alcohol dependence is a severe mental disorder, with high relapse rates and high mortality. Alcohol dependent patients with co-morbid anxiety disorders are particularly prone to relapse during the first three months of treatment. These patients may therefore require additional medical and psychological attention.

[Detoxification of patients with GHB dependence]. / Detoxificatie van patiënten met GHB-afhankelijkheid.

BACKGROUND: A new detoxification method for GHB dependence was developed recently in the Netherlands. The method involves the use of pharmaceutical GHB. AIM: To describe the characteristics of GHB dependent inpatients, the course of the detoxification process and patients' progress in the three months following inpatient detoxification. METHOD: 229 GHB dependent patients were monitored during and after inpatient detoxification. Records were kept of the psychiatric symptoms, withdrawal symptoms and relapses. RESULTS: The average age of the patients was 29 years; 69% of the patients were male. They reported severe symptoms of co-occurring depression and anxiety. Detoxification was successful in 86% of the patients and, on a whole, the procedure ran smoothly, without complications. However, within three months following detoxification two-thirds of the patients had relapsed and were again taking GHB. CONCLUSION: Pharmaceutical GHB can be used as an alternative to the benzodiazepine method for detoxifying patients with GHB dependence. However, the high relapse rates following detoxification are of great concern.

Damage in the dorsal striatum alleviates addictive behavior.

The ventral striatum has been assigned a major role in addictive behavior. In addition, clinical lesion studies have described involvement of the insula and globus pallidus. To the best of our knowledge, this is the first report of alleviation of alcohol and nicotine addiction after a cerebrovascular incident in the dorsal striatum. The patient was still abstinent from alcohol and nicotine at follow-up. This observation suggests that the dorsal striatum may play a critical role in addiction to alcohol and nicotine.