Shaping and shifting schemas on supervised injectable opioid treatment: findings from a cross-sectional qualitative study in two German treatment facilities.

BACKGROUND: Supervised injectable opioid treatment (SIOT) is a promising alternative for people living with opioid use disorder (OUD) who have not sufficiently benefitted from oral opioid substitution treatment. Yet, SIOT utilization remains limited in Germany. We propose that this is due to beliefs, or schemas, on SIOT among people living with OUD. Drawing from medical sociology and social psychology, this study explores the emergence and evolution of such schemas on SIOT. METHODS: We conducted semi-structured interviews with 34 individuals currently in or eligible for SIOT in two German outpatient treatment facilities and paralleled an inductive qualitative content analysis with the exploration of individual cases. RESULTS: The analysis revealed that peer-to-peer interaction and individuals' practical experiences in therapy are crucial in constructing and changing idiosyncratic and shared schemas of SIOT. When facing ambiguous information, cognitive strategies like subtyping served to mitigate uncertainty. CONCLUSION: This research has important practical implications for integrating experiential knowledge into clinical care and improve information sharing among people living with OUD. A nuanced understanding of the complex network of informal advice-seeking and -giving among people living with OUD is indispensable to adequately expand treatment modalities of proven effectiveness.

Psychiatric and non-psychiatric patients during the midst of Covid-19: Pandemic distress, psychosis and the belief in conspiracy theories.

BACKGROUND: The COVID-19 pandemic was associated with increased levels of psychological distress in the general population, at the same time providing a perfect breeding ground for conspiracy beliefs. Psychiatric patients are considered as a population with an increased vulnerability for stressful events, and conspiracy beliefs show overlaps with paranoid ideations. The aim of the present study was to investigate if psychiatric patients experienced higher levels of pandemic distress than non-psychiatric patients, if they were more prone to conspiracy beliefs and if pandemic distress as well as other mental health variables were associated with believing in conspiracy theories. METHODS: Indicators for mental health (pandemic distress, depressive symptoms, general anxiety symptoms, perceived stress) and indicators for believing in conspiracy theories were assessed within psychiatric (n = 73) and non-psychiatric patients (n = 29) during the midst of the pandemic. RESULTS: Psychiatric patients reported higher levels of pandemic distress than non-psychiatric patients. Conspiracy measurements correlated positively with pandemic distress, but not with anxiety and depression. No differences were found between psychiatric patients with or without psychotic disorder and non-psychiatric patients in regard to conspiracy measurements. CONCLUSION: Our findings suggest a higher susceptibility of psychiatric patients to pandemic distress, but not an increased level of believing in conspiracy theories. The common notion that people suffering from psychosis are more likely to believe in conspiracy theories was not supported. Furthermore, distress caused by a specific event and not anxiety per se seems to be related to the degree of conspiracy beliefs.

Exploring Patients' Perceptions on Injectable Opioid Agonist Treatment: Influences on Treatment Initiation and Implications for Practice.

INTRODUCTION: Injectable opioid agonist treatment (iOAT) with diacetylmorphine is an effective option for individuals previously considered non-responsive to opioid substitution treatment. Despite implementation in Canada and several European countries, relatively few eligible people choose to initiate iOAT. To better understand what encourages or deters prospective patients from initiating iOAT, the current study explores patients' perceptions on iOAT and how these influence therapy initiation in practice. METHODS: We conducted 34 semi-structured interviews with individuals currently in or eligible for iOAT in two German outpatient iOAT clinics. Transcripts were analysed following qualitative content analysis, with development of inductive categories and use of consensual coding. For member checking, we consulted individuals with lived experiences prior to data collection and publication. RESULTS: Participants based their choice to initiate iOAT on the perceived implications of the treatment on one's daily life and individual recovery. Participants were encouraged to initiate iOAT due to the therapy's perceived potential in reducing cravings and substance use, its positive health consequences, and due to the image of iOAT as a path towards abstinence. Regarding deterring perceptions, participants feared a profound impairment of daily life due to factors such as the daily visits to the clinic, were concerned about whether iOAT would sufficiently promote or even impede one's recovery, and described negative health effects. CONCLUSION: Perceptions found in this study profoundly influenced participants' decisions on iOAT enrolment and contextualize the previous literature. The study reveals the dynamic coexistence of different perceptions about iOAT and sheds light on the inner-group stigmatization of iOAT. Practitioners and future research should acknowledge the complexities found in the current study in order to exploit the full potential of effective treatment modalities such as iOAT.

Supervised on-site dosing in injectable opioid agonist treatment-considering the patient perspective. Findings from a cross-sectional interview study in two German cities.

BACKGROUND: Injectable opioid agonist treatment (iOAT) is an effective option to support people living with opioid use disorder (OUD) who have not sufficiently benefitted from oral OAT. However, iOAT has been criticised based on theoretical and practical grounds for its dosing policies: Current regulations demand supervised, on-site application and require patients to frequently visit their treatment facility. The current study aims to investigate how patients experience on-site application and derive strategies to enhance the acceptability and effectiveness of iOAT-delivery. METHODS: This article is based on semi-structured interviews with 27 individuals currently or previously in iOAT in two German outpatient iOAT-clinics. We undertook an inductive qualitative content analysis, which included blinded, independent coding and the analysis of individual cases. RESULTS: Comments regarding on-site application and daily visits to the clinic were grouped into positive and negative aspects, iOAT as the best alternative option, facilitators of daily visits, and suggestions for improvement. Positive aspects took the factors stability and social support in regard. Negative aspects ranged from general inconveniences to major impediments to individuals' daily lives and towards achieving psychosocial goals. Participants reported rigorous adherence to iOAT's treatment regime, often due to a perceived lack of alternative options. Meeting iOAT's demands was eased by the patients' coping-strategies and through facilitating measures implemented by iOAT-clinics. Despite acknowledgement of the potential detriments from easing regulations, take-home arrangements were frequently suggested by participants to improve iOAT. CONCLUSIONS: Being required to attend the clinic for supervised iOAT-application is not experienced uniformly. While clinics can support their patients to cope with strict regulations, alternative approaches to iOAT-application should be considered to accommodate patients' individual needs. Examples from other treatment modalities (e.g., remote supervision and delivery services) might aid to reconcile individualisation while providing adequate safety measures and improve iOAT in the long term.

[Utilization of a Specialized Outpatient Service for Parents with Mental Disorders]. / Inanspruchnahme einer Spezialsprechstunde für psychisch kranke Eltern.

BACKGROUND: Patients with mental disorders have a high need for support during the peripartum period. Only few outpatient services have specialized on parents with mental disorders. This study assesses a newly established outpatient unit. METHODS: We analyzed the population utilizing the outpatient service for parents with psychiatric disorders (N=279) at the psychiatric university hospital of Charité at St. Hedwig-hospital in Berlin, Germany, from June 2017 until December 2021. RESULTS: The service was mainly utilized by individuals with affective disorders, a higher education and good compliance. Patients with migration background started psychotherapy less often. DISCUSSION: The data indicate a good acceptance of a specialized outpatient unit for parents with psychiatric disorders; however, it was mainly utilized by individuals with a higher socioeconomic status and less commonly by individuals with severe mental illness. More specialized treatment units for parents would be desirable.

No party, no drugs? Use of stimulants, dissociative drugs, and GHB/GBL during the early COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is presumably having an impact on the consumption of psychoactive substances. Social distancing and lockdown measures may particularly affect the use of "party drugs" (e.g., stimulants, dissociatives, and GHB/GBL) through the absence of typical use settings. We aimed to analyse the use patterns of those substances and underlying motivations before and during the pandemic. METHODS: A subsample of 1,231 users of stimulants (amphetamine, methamphetamine, MDMA/ecstasy, cocaine), dissociative drugs (ketamine, dextromethorphan, PCP), and GHB/GBL was assessed from 30th April to 4th August 2020 as part of the Corona Drug Survey, a cross-sectional international online survey in five languages that included a total of 5,049 participants. The reported use of distinct substances and the underlying motivations were ascertained before (retrospectively) and during the pandemic. Furthermore, associations between drug use as a coping mechanism, pandemic-related stressors, and substance use were examined. RESULTS: Regarding the reported frequency of use during the pandemic, 48.0-64.8% of the sample ceased or decreased, 11.9-25.5% maintained, and 23.6-29.1% increased their consumption. MDMA/ecstasy showed the strongest decrease and GHB/GBL and dissociatives the highest increase. Participants reported that price, quality, and supply were mostly unaffected by the pandemic. The most common motivations before and during the pandemic were mood-related factors, such as a desire to feel exhilarated, euphoric, high, or buzzed. The relevance of social purposes and mood-related motivators declined during the pandemic, whereas dealing with boredom increased. Overall, 16.4-35.6% perceived drug use as helpful for dealing with pandemic-related stressors, which were associated with an increased consumption frequency. CONCLUSION: The early stage of the COVID-19 pandemic was associated with major changes in the use of "party drugs". Those who increased their level of drug use and perceived it as a coping strategy in particular might be targeted with adaptive preventive and therapeutic measures.

Cannabis use during the early COVID-19 pandemic: Use patterns, predictors, and subjective experiences.

Background: Even in the early stages, global crises such as the COVID-19 pandemic lead to serious dislocations of social life, secondary adjustment reactions to external restrictions and individual concerns. Coping mechanisms may also include dysfunctional strategies like an increase of drug use. Considering the wide-spread use of cannabis, the aim of this study was to elucidate the interplay of social restrictions, psychopathology, concerns related to the pandemic in addition to the users' experiences, motivations and consumption quantities during the early COVID-19 pandemic. It was presumed that cannabis intake would increase during the early phase of the crisis and that consumption quantities would be related to corona-related restrictions, concerns as well as subjective substance effects and psychopathology. Materials and methods: As part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages, consumption quantities and patterns of cannabis use in the early phase of the pandemic from April to August 2020 were examined. Participants retrospectively rated restrictions and concerns related to the pandemic, motives of cannabis use prior to and during 1 month the pandemic, and subjective consumption effects. Results: Cannabis use behavior showed no significant differences when consumption quantities prior and during 1 month after the COVID-19 outbreak were compared. Higher quantities of cannabis intake prior and during 1 month of the pandemic as well as more corona-related concern were associated with an increased perception of positive effects of cannabis during the pandemic. Predictors of its use during 1 month of pandemic were higher pre-pandemic consumption quantity, older age, quarantinization, a lesser degree of being affected by negative effects of the pandemic and a stronger subjective experience of corona-related positive effects of cannabis. Comparisons of the motives for cannabis intake in the pre-pandemic versus the pandemic period showed that all rationales for consumption were reported less frequently, except boredom. Conclusion: Frequencies of cannabis intake remained relatively stable in the early pandemic phase. Risk factors for increased use seem related to habitual consumption patterns that become more prominent under quarantinization. The use of cannabis as a dysfunctional coping strategy might not be amenable via self-report and should therefore receive special attention in clinical contexts.

Psychedelic Experiences During the Early COVID-19 Pandemic: Findings From an International Online Survey.

Introduction: The current corona virus disease (COVID-19) pandemic has caused a serious global health crisis that has affected large parts of the public and private life worldwide, including the use of psychoactive substances. In this study, we investigated the effect of the COVID-19 pandemic on the use of serotonergic psychedelics, i.e., the settings in which people use psychedelics, the motives of usage, and the subjective quality of psychedelic experiences. Methods: The study was part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages (English, German, Spanish, Italian, and Korean) carried out during the early phase of the pandemic from April to August 2020. Participants were asked to retrospectively rate settings and motives of psychedelic substance use before the pandemic and in the last 4 weeks during the pandemic, as well as changes in psychedelic experiences. Results: Of n = 1,375 participants that reported the use psychedelics in 2019 or 2020, n = 642 (46.6%) also took psychedelics during the pandemic. During the pandemic, participants used psychedelics significantly less often in settings that were outside their home. Top motives to use psychedelics were comparable before and during the pandemic, but participants consumed less out of curiosity, to celebrate, or because friends took it, and more out of boredom. An increase in positively connoted, often pro-social experiences was observed. Two thirds of participants who used psychedelics during the pandemic claimed that psychedelics had helped them to deal better with the corona pandemic at least slightly. Discussion: Changes in setting and motives were mostly in line with restrictions caused by control measures to contain the spread of the virus. The unexpected increase in positively connoted experiences possibly reflects a favorable interaction of environmental macro- and individual micro-contexts during the pandemic (e.g., by reducing the use in more uncontrolled recreational settings or by encouraging a strong self-selection of substance users due to the expectation of "bad trips"). Increased pro-social feelings under psychedelics might reflect a desire for social interactions in times of social distancing and pandemic-related stress and anxiety.

Predictors of Alcohol Consumption Among Younger Adults During the First Phase of the COVID-19 Pandemic.

Background: The COVID-19 pandemic may lead to negative mental health effects but the effect on alcohol consumption among younger adults is unclear. We assess predictors of change in alcohol consumption during the first phase of the COVID-19 pandemic among younger adults. Methods: This cross-sectional internet-based survey was part of an overarching project, the Corona Drug Survey, which was conducted from April 30 to August 4, 2020. Participants of any sex and ≥18 years old were included. The primary outcome measure was change in alcohol consumption during the early COVID-19 pandemic. We implemented an ordinal logistic regression to assess the effect (odds ratio [OR] and 95% confidence interval [CI]) of the following predictors: quarantine restrictions on leaving the residence, number of individuals in the household, problematic alcohol consumption before the pandemic (CAGE [cutting down, annoyance by criticism, guilty feeling, and eye-opener] score), personal concern regarding the pandemic, age, and sex. Results: 3,321 participants with a mean age of 32 (SD: 13) years were included in this study. 70.4% of participants reported less or unchanged alcohol consumption in the recent 4 weeks of the pandemic compared to before the pandemic. A higher number of individuals in the household was associated with a reduced alcohol consumption (OR = 0.869; 95% CI = 0.815-0.927). No quarantine restrictions on leaving the residence (OR = 1.593; 95% CI = 1.397-1.817), a higher age (1.006; 1.001-1.011), and female sex (compared to males: 1.206; 1.062-1.371) were associated with an increase in alcohol consumption. The CAGE score before the pandemic (OR = 0.983; 95% CI = 0.931-1.037) and the pandemic concern (0.927; 0.857-1.003) were not associated with a significant change in alcohol consumption. Celebrations were no longer frequent drinking occasions during the pandemic compared to before the pandemic. The majority of participants (60.9%) did not use alcohol drinking as a coping mechanism to mitigate negative effects of the pandemic. Interpretation: In this cohort of younger adults with fewer celebratory drinking occasions, restrictions on leaving the residence and the number of persons in the household were the strongest predictors of reduced alcohol consumption during the early phase of the pandemic.

New Approaches in Drug Dependence: Opioids.

Purpose of Review: This article aims to provide an overview of standard and adjunctive treatment options in opioid dependence in consideration of therapy-refractory courses. The relevance of oral opioid substitution treatment (OST) and measures of harm reduction as well as heroin-assisted therapies are discussed alongside non-pharmacological approaches. Recent Findings: Currently, recommendation can be given for OST with methadone, buprenorphine, slow-release oral morphine (SROM), and levomethadone. Heroin-assisted treatment using diamorphine shall be considered as a cost-effective alternative for individuals not responding to the afore-mentioned opioid agonists in order to increase retention and reduce illicit opioid use. The modalities of application and the additional benefits of long-acting formulations of buprenorphine should be sufficiently transferred to clinicians and the eligible patients; simultaneously methods to improve planning of actions and self- management need to be refined. Regarding common primary outcomes in research on opioid treatment, evidence of the effectiveness of adjunctive psychological interventions is scarce. Summary: Maintaining a harm reduction approach in the treatment of opioid addiction, a larger range of formulations is available for the prescribers. Embedding the pharmacological, ideally individualized treatment into a holistic, structure-giving concept also requires a reduction of fragmentation of ancillary services available, drug policies, and treatment philosophies on a global scale.

Alcohol and Dementia - What is the Link? A Systematic Review.

BACKGROUND: Dementia is a globally increasing health issue and since no cure is currently available, prevention is crucial. The consumption of alcohol is a controversially discussed risk factor for dementia. While many previously published epidemiological studies reported a risk reduction by light to moderate alcohol consumption, there is no persuasive model of an underlying biochemical mechanism. The purpose of this article is to review current models on alcohol neurotoxicity and dementia and to analyze and compare studies focusing on the epidemiological link between alcohol consumption and the risk of dementia. METHODS: The electronic database Pubmed was searched for studies published between 1994 and 2019 concerning the topic. RESULTS: Available epidemiological studies are not sufficient to verify a protective effect of alcohol on dementia development.

Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals.

Addiction has been proposed as a 'reward deficient' state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.

Neural and neurocognitive markers of vulnerability to gambling disorder: a study of unaffected siblings.

Psychological and neurobiological markers in individuals with gambling disorder (GD) could reflect transdiagnostic vulnerability to addiction or neuroadaptive consequences of long-term gambling. Using an endophenotypic approach to identify vulnerability markers, we tested the biological relatives of cases with GD. Male participants seeking treatment for GD (n = 20) were compared with a male control group (n = 18). Biological siblings of cases with GD (n = 17, unrelated to the current GD group) were compared with a separate control group (n = 19) that overlapped partially with the GD control group. Participants completed a comprehensive assessment of clinical scales, neurocognitive functioning, and fMRI of unexpected financial reward. The GD group displayed elevated levels of self-report impulsivity and delay discounting, and increased risk-taking on the Cambridge Gamble Task. We did not observe impaired motor impulsivity on the stop-signal task. Siblings of GD showed some overlapping effects; namely, elevated impulsivity (negative urgency) and increased risk-taking on the Cambridge Gamble Task. We did not observe any differences in the neural response to win outcomes, either in the GD or sibling analysis compared with their control group. Within the GD group, activity in the thalamus and caudate correlated negatively with gambling severity. Increased impulsivity and risk-taking in GD are present in biological relatives of cases with GD, suggesting these markers may represent pre-existing vulnerability to GD.

GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models.

Preliminary studies have suggested that γ-aminobutyric acid type A (GABAA) receptors, and potentially the GABAA α5 subtype, are deficient in autism spectrum disorder (ASD). However, prior studies have been confounded by the effects of medications, and these studies did not compare findings across different species. We measured both total GABAA and GABAA α5 receptor availability in two positron emission tomography imaging studies. We used the tracer [11C]flumazenil in 15 adults with ASD and in 15 control individuals without ASD and the tracer [11C]Ro15-4513 in 12 adults with ASD and in 16 control individuals without ASD. All participants were free of medications. We also performed autoradiography, using the same tracers, in three mouse models of ASD: the Cntnap2 knockout mouse, the Shank3 knockout mouse, and mice carrying a 16p11.2 deletion. We found no differences in GABAA receptor or GABAA α5 subunit availability in any brain region of adults with ASD compared to those without ASD. There were no differences in GABAA receptor or GABAA α5 subunit availability in any of the three mouse models. However, adults with ASD did display altered performance on a GABA-sensitive perceptual task. Our data suggest that GABAA receptor availability may be normal in adults with ASD, although GABA signaling may be functionally impaired.

First evaluation of PET-based human biodistribution and radiation dosimetry of 11C-BU99008, a tracer for imaging the imidazoline2 binding site.

BACKGROUND: We measured whole body distribution of 11C-BU99008, a new PET biomarker for non-invasive identification of the imidazoline2 binding site. The purpose of this phase I study was to evaluate the biodistribution and radiation dosimetry of 11C-BU99008 in healthy human subjects. METHODS: A single bolus injection of 11C-BU99008 (296 ± 10.5 MBq) was administered to four healthy subjects who underwent whole-body PET/CT over 120 min from the cranial vertex to the mid-thigh. Volumes of interest were drawn around visually identifiable source organs to generate time-activity curves (TAC). Residence times were determined from time-activity curves. Absorbed doses to individual organs and the whole body effective dose were calculated using OLINDA/EXM 1.1 for each subject. RESULTS: The highest measured activity concentration was in the kidney and spleen. The longest residence time was in the muscle at 0.100 ± 0.023 h, followed by the liver at 0.067 ± 0.015 h and lungs at 0.052 ± 0.010 h. The highest mean organ absorbed dose was within the heart wall (0.028 ± 0.002 mGy/MBq), followed by the kidneys (0.026 ± 0.005 mGy/MBq). The critical organ was the heart wall. The total mean effective dose averaged over subjects was estimated to be 0.0056 ± 0.0004 mSv/MBq for an injection of 11C-BU99008. CONCLUSIONS: The biodistribution of 11C-BU99008 has been shown here for the first time in humans. Our dosimetry data showed the total mean effective dose over all subjects was 0.0056 ± 0.0004 mSv/MBq, which would result in a total effective dose of 1.96 mSv for a typical injection of 350 MBq of 11C-BU99008. The effective dose is not appreciably different from those obtained with other 11C tracers.

Evaluation of 11C-BU99008, a PET Ligand for the Imidazoline2 Binding Site in Human Brain.

The imidazoline2 binding site (I2BS) is thought to be expressed in glia and implicated in the regulation of glial fibrillary acidic protein. A PET ligand for this target would be important for the investigation of neurodegenerative and neuroinflammatory diseases. 11C-BU99008 has previously been identified as a putative PET radioligand. Here, we present the first in vivo characterization of this PET radioligand in humans and assess its test-retest reproducibility. Methods: Fourteen healthy male volunteers underwent dynamic PET imaging with 11C-BU99008 and arterial sampling. Six subjects were used in a test-retest assessment, and 8 were used in a pharmacologic evaluation, undergoing a second or third heterologous competition scan with the mixed I2BS/α2-adrenoceptor drug idazoxan (n = 8; 20, 40, 60, and 80 mg) and the mixed irreversible monoamine oxidase type A/B inhibitor isocarboxazid (n = 4; 50 mg). Regional time-activity data were generated from arterial plasma input functions corrected for metabolites using the most appropriate model to derive the outcome measure VT (regional distribution volume). All image processing and kinetic analyses were performed in MIAKAT. Results: Brain uptake of 11C-BU99008 was good, with reversible kinetics and a heterogeneous distribution consistent with known I2BS expression. Model selection criteria indicated that the 2-tissue-compartment model was preferred. VT estimates were high in the striatum (105 ± 21 mL⋅cm-3), medium in the cingulate cortex (62 ± 10 mL⋅cm-3), and low in the cerebellum (41 ± 7 mL⋅cm-3). Test-retest reliability was reasonable. The uptake was dose-dependently reduced throughout the brain by pretreatment with idazoxan, with an average block across all regions of about 60% (VT, ∼30 mL⋅cm-3) at the highest dose (80 mg). The median effective dose for idazoxan was 28 mg. Uptake was not blocked by pretreatment with the monoamine oxidase inhibitor isocarboxazid. Conclusion:11C-BU99008 in human PET studies demonstrates good brain delivery, reversible kinetics, heterogeneous distribution, specific binding signal consistent with I2BS distribution, and good test-retest reliability.

Paliperidone and pregnancy-an evaluation of the German Embryotox database.

Schizophrenic or schizoaffective disorders often occur in early adulthood and thus affect women of childbearing age. For paliperidone information about reproductive safety is wanting. Therefore, we evaluated data from the German Embryotox pharmacovigilance institute regarding paliperidone therapy during pregnancy. The German Embryotox pharmacovigilance institute offers risk assessment on drug use in pregnancy and documents the outcome of more than 3500 drug-exposed pregnancies per year. In our study, we analyze the outcome of all pregnancies with paliperidone exposure, which have been assessed by our institute between January 2007 and June 2016. Of the 17 prospectively assessed pregnancies, 14 resulted in 15 live-born children (including one pair of twins). None of the infants presented with major congenital malformations. There were two spontaneous abortions at gestational weeks 6 and 11, respectively, and one elective termination due to personal reasons. Sixty-five percent of the pregnant women smoked cigarettes throughout pregnancy, 17% consumed alcohol. Five children were born prematurely (< 37 gestational weeks) and four were small for gestational age, each group including the twins. The results of our study suggest that paliperidone may be administered during pregnancy. The increased rate of prematurity and small for gestational age children can at least partially be explained by other risk factors. Psychiatric and obstetric close monitoring as well as additional medical and social support are recommended to ensure a healthy pregnancy course in patients with a severe mental illness.

Using Baclofen to Explore GABA-B Receptor Function in Alcohol Dependence: Insights From Pharmacokinetic and Pharmacodynamic Measures.

Background: The role of GABA-B neurotransmission in addiction has recently received increased attention, with clinical trials indicating that baclofen, a GABA-B receptor agonist, may reduce alcohol consumption, craving and promote abstinence. However, the optimal dose to treat alcohol dependence is unclear with patients requesting and tolerating much higher doses of baclofen, compared with other clinical uses. We assessed the pharmacokinetics and pharmacodynamics (PK/PD) of baclofen to provide insight into GABA-B sensitivity in this patient group, relative to controls. Methods: Male healthy volunteers (controls, n = 12) and abstinent alcohol dependent individuals (AD, n = 8) received single oral doses of baclofen or placebo in a 3-way crossover design. Controls received placebo/10 mg/60 mg baclofen in a randomized, double-blind design, AD received placebo/60 mg/90 mg baclofen in a single-blind design. PK/PD measures were recorded at baseline and multiple time-points up to 6 h post-dosing, including plasma baclofen, plasma growth hormone (GH), Subjective High Assessment Scale (SHAS) and biphasic alcohol effects scale (BAES). Repeated measures ANOVA analysis explored "change from baseline" dose, time, group, and interaction effects, t-tests compared peak effects. Results: Dose-dependent effects of baclofen on PK and PD measures were observed in both control and AD groups. Whilst there were no significant group differences in any baclofen PK parameters (t 1/2, t max , C max , AUC), marked differences in PD effects were clearly evident. In controls, 60 mg baclofen significantly increased total SHAS and BAES scores, and significantly increased plasma GH levels compared with placebo, with peak effects at 60-120 min, in line with its PK profile. In AD, 60 mg baclofen had limited effects on these parameters; SHAS scores, BAES scores and plasma GH levels were significantly blunted compared with controls (significant group*time interactions P = 0.0014, 0.0015 and P < 0.0001, respectively). Conclusions: Our study shows blunted sensitivity to baclofen in AD relative to controls, with no difference in PK suggesting a lower GABA-B receptor sensitivity. This may explain why higher baclofen doses are requested and tolerated in the treatment of alcohol dependence. Our data has implications for choice of dose in future clinical trials in AD and possibly other substances of dependence.

Transient congenital dilated cardiomyopathy after maternal R-CHOP chemotherapy during pregnancy.

Pregnancy-associated diffuse large B-cell lymphoma (DLBCL) is a rare event. Experience regarding fetal effects of maternal treatment during pregnancy is limited. Cardiotoxicity is a known adverse effect of some antineoplastic agents especially of doxorubicin. We report a case of pregnancy-associated DLBCL, which was treated between gestational week 26 and 33 with three cycles of R-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone combined with rituximab). At gestational age 34 2/7 she delivered a male infant who was admitted to neonatal care due to cardiomyopathy. In the absence of other explanations it was interpreted as a direct toxic effect of maternal chemotherapy. At age 6 months the boy's cardiac output had normalized. This case report is the first presenting congenital cardiomyopathy after maternal R-CHOP during pregnancy. Since especially anthracyclines are known to cause acute and chronic cardiotoxicity in treated patients, the most probable explanation for neonatal cardiomyopathy in this case is doxorubicin.

Nalmefene Reduces Reward Anticipation in Alcohol Dependence: An Experimental Functional Magnetic Resonance Imaging Study.

BACKGROUND: Nalmefene is a µ and δ opioid receptor antagonist, κ opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol-dependent individuals with "high-risk drinking levels" to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomized, double-blind, placebo-controlled, within-subject crossover design we aimed to determine the effect of a single dose of nalmefene on striatal blood oxygen level-dependent (BOLD) signal change during anticipation of monetary reward using the monetary incentive delay task following alcohol challenge. METHODS: Twenty-two currently heavy-drinking, non-treatment-seeking alcohol-dependent males were recruited. The effect of single dose nalmefene (18 mg) on changes in a priori defined striatal region of interest BOLD signal change during reward anticipation compared with placebo was investigated using functional magnetic resonance imaging. Both conditions were performed under intravenous alcohol administration (6% vol/vol infusion to achieve a target level of 80 mg/dL). RESULTS: Datasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal region of interest compared with placebo. Nalmefene did not alter brain perfusion. CONCLUSIONS: Nalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene's actions on opioid receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy.