12129 Background: Chemotherapy-induced neurotoxicity is a frequent adverse effect of paclitaxel (PTX). It reduces quality of life and often necessitates treatment modifications. The objective of this clinical trial was to determine the safety and efficacy of lithium (Li + ) co-treatment on chemotherapy-induced neurotoxicity in breast cancer patients treated with PTX. Methods: Multicenter, randomized, double-blind, placebo-controlled phase-2 trial (parallel-group design) conducted in eight primary care centers in Germany between August 2022 and July 2024. Eligible breast cancer patients aged 18-70 years, with no pre-existing polyneuropathy and to be treated with PTX were randomized 1:1 to either oral Li + or placebo with sham dose adjustments. The intervention started 10-14 days prior to the first and lasted until three days after the last PTX infusion. Results: A total of 94 patients were enrolled, 86 patients were randomized and 78 were analyzed according to the intention-to-treat principle. Targeted Li + trough serum concentrations of 0.5 to 0.8mmol/l were reliably reached prior to PTX therapy. The total neuropathy score reduced (TNSr) was 0.5 points higher in the placebo group than in the Li + group (95% CI 1.6 to -0.6, not significant), while serum neurofilament light chain levels showed no difference. Structural MRI showed slightly higher total intracranial volume in the Li⁺ group, but no difference in hippocampal volume. Cognitive testing using the CANTAB indicated a strong trend towards better performance in hippocampus-dependent tasks, including delayed matching to sample and spatial working memory for the Li + group. The patient reported outcome measures (PROM) completion rates were high (baseline 99%, endpoint 95%). Patients receiving Li⁺ consistently reported higher quality of life and less pain scores on the EORTC QLQ-C30 during and after therapy, with between-group differences of 11 AU (95% CI 18 to 4) for global health status and -14 AU (95% CI −27 to -0.2) for pain, exceeding established minimal clinically important differences. The latter finding was supported by a lower reported intake of pain medication in the Li + group of 54% vs 70% in the placebo group. Eleven serious adverse events were reported in the trial, six in the placebo group and five in the Li + group. Patients in the Li + group experienced fewer adverse events compared to patients in the placebo group with a relative risk reduction of 26% for any CTCAE grade and 45% for grade ≥ 3. Conclusions: Among breast cancer patients receiving PTX chemotherapy co-treatment with Li + was not superior to placebo for the development of polyneuropathy as measured by TNSr. However, there were better patient-reported outcomes including quality of life and pain, as well as lower rates of adverse events. These observations warrant confirmation in a larger phase-3 interventional trial. Clinical trial information: DRKS00027165.

INTRODUCTION:Adverse environments during pregnancy impact neurodevelopment including cognitive abilities of the developing children. The mediating biological alterations are not fully understood. Maternal stress may impact the neurotrophic regulation of the offspring as early as in utero and at birth. Brain-derived neurotrophic factor (BDNF) is essential for neurodevelopment. Short-term higher levels of BDNF in mice upon stressors associate with lower BDNF later in life, which itself associates with depression in animals and humans. Stress including glucocorticoids may impact BDNF, but there is a lack of data at birth. This study investigated if stress near term associates with fetal BDNF at birth in humans. METHODS:Pregnant women near term who underwent primary cesarean sections (at 38.80±0.64 weeks), were included in this study (n=41). Stress at the end of pregnancy was assessed before the cesarean section by determining maternal depressive symptoms (EDPS), maternal state and trait anxiety (STAI-S and STAI-T), maternal prenatal distress (PDQ), stress over the past month (PSS), prenatal attachment to the offspring (PAI), maternal social support (F-Sozu), maternal early life stress (CTQ), socioeconomic status, and the glucocorticoids cortisol and cortisone (n=40) in amniotic fluid at birth. The association with fetal BDNF was analyzed. Cord blood serum of n=34 newborns at birth was analyzed for BDNF and newborn anthropometrics (weight, length and head circumference per gestational age at birth) were assessed. The association of fetal BDNF with anthropometrics at birth was analyzed. RESULTS:After a BDNF-outlier (>3 SD) was removed, higher fetal BDNF associated significantly with maternal depressive symptoms (r=0.398, p=0.022), with lower socioeconomic status as assessed by the average number of people per room in the household (r=0.526, p=0.002) and with borderline significance with net income per person in the household (r=-0.313, p=0.087) in the bivariate analyses. In multivariable analysis, BDNF stayed positively associated with maternal depressive symptoms (β=0.404, 95% CI [7.057, 306.041], p=0.041) and lower net income per person in the household (β=-0.562, 95% CI [-914.511, -60.523], p=0.027) when controlling for maternal age, maternal pre-pregnancy BMI, fetal sex and gestational age. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed in bivariate analyses or in multivariable analyses when controlling for maternal BMI and fetal sex. CONCLUSION:Maternal depressive symptoms and lower socioeconomic status associated with higher fetal BDNF when controlling for confounders. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed. Further studies should investigate how early altered BDNF associate with the development and possibly psychopathology of the offspring.

Background Brain-derived neurotrophic factor (BDNF) is a protein important for synaptic plasticity and formation of memory. It is suggested to play an important role in the development of psychiatric disorders like post-traumatic stress disorder (PTSD). Individuals with PTSD usually show decreased BDNF levels in serum. Physical exercise has shown to be effective in increasing serum BDNF levels. Objective As the most beneficial form of exercise to raise serum BDNF levels in individuals with PTSD is yet to be determined, we compared two training protocols and their effects on BDNF release. We expected that a training with higher intensity increases BDNF serum levels more than a low intensity training (LIT). Method 40 participants (80% female) diagnosed with PTSD were randomized to either high-intensity interval training (HIIT) or a low intensity training group (LIT). They underwent a 12-day training period. We measured serum BDNF levels pre- and post-exercise on first and last intervention day. BDNF was controlled for platelet counts. Results In the HIIT group there was a significant increase in serum BDNF post-exercise on both days measured, respectively when controlled for platelets. The increase was transient. Both groups did not show an increase in serum BDNF over the course of the 12-day training period. Conclusion A single session of HIIT raised serum BDNF levels in individuals with PTSD transiently. Neither HIIT nor LIT raised serum BDNF levels over the course of 12 days.

Introduction: At the maternal-fetal interface in pregnancy, stress during pregnancy can lead to an increased vulnerability to later psychopathology of the fetus. Potential mediators of this association have scarcely been studied and may include early alterations of fetal brain-derived neurotrophic factor (BDNF). Amniotic fluid is of particular interest for effects on fetal endocrine alterations, as the assessment in amniotic fluid allows for measurements over a time integral. This study hypothesized that maternal psychometrics, socioeconomic status and glucocorticoids are related to BDNF levels in amniotic fluid at birth. The association of fetal BDNF with newborn anthropometrics was tested. Methods: Women near term who underwent elective cesarean section and their newborns were investigated (n = 37). Maternal psychometrics, socioeconomic status and glucocorticoids (the sum of cortisol and cortisone) in amniotic fluid at birth were analyzed for an association with fetal BDNF in amniotic fluid at birth. Newborn anthropometrics were assessed by length, weight, head circumference and gestational age at birth. Results: In bivariate analysis, maternal psychometrics and socioeconomic status were not related to fetal BDNF in amniotic fluid at birth. The sum of cortisol and cortisone related to increased fetal BDNF in amniotic fluid at birth (r = 0.745, p < 0.001). BDNF in amniotic fluid was associated negatively with fetal birth weight per gestational age (r = -0.519, p < 0.001), length per gestational age (r = -0.374, p = 0.023), head circumference per gestational age (r = -0.508, p = 0.001), but not with gestational age at birth. In multiple regression analysis, the sum of cortisol and cortisone (p < 0.001) and birth weight per gestational age (p = 0.012) related to higher fetal BDNF levels in amniotic fluid at birth (R2 = 0.740, p < 0.001) when controlling for fetal sex and maternal age. Head circumference per gestational age predicted fetal BDNF with borderline significance (p = 0.058) when controlling for confounders. Conclusion: Glucocorticoids in amniotic fluid were positively associated with high fetal BDNF at birth, which may be an adaptive fetal response. Maternal psychological variables and socioeconomic status did not link to fetal BDNF. Birth weight and head circumference per gestational age were inversely associated with fetal BDNF at birth, which may represent a compensatory upregulation of BDNF in fetuses with low anthropometrics. Longitudinal studies are needed to assess the role of stress during pregnancy on later offspring development. The

Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine implicated in the pathogenesis of major depressive disorder (MDD). In MDD, serum BDNF levels are attenuated. Healthy adults show BDNF elevation after exercise. To investigate activity-dependent BDNF elevation in MDD, thirty-seven participants with partially remitted MDD were allocated to either a bout of strenuous or light activity. Serum was collected before and after the intervention. BDNF was measured using a highly sensitive and specific enzyme-linked immunosorbent assay. Significant BDNF elevation in the strenuous activity group emerged. This study confirms exercise-dependent serum BDNF elevation in MDD. Preregistration: German Clinical Trials Register (DRKS0001515).

The 2018 European Union (EU) approved weekly and monthly subcutaneous buprenorphine depot injection (BUP-XR), for opioid substitution medication proved to offer some specific treatment benefits. The present study examines the process of switching from buprenorphine sublingual tablets (BUP-SL) to BUP-XR from a patient's point of view. In total, nine patients were surveyed by means of an open-answer questionnaire regarding course and side effects of the medication switch. Six of these patients were surveyed in more detail under BUP-SL, as well as 4 and 16 weeks after the switch to BUP-XR by means of a test battery of questions on socio-demography, withdrawal symptoms, craving, physical well-being, treatment satisfaction and concomitant use of illegal substances. Patients reported significant worse physical well-being and lower treatment satisfaction in 4 weeks compared with 16 weeks after the medication switch to the BUP-XR. Furthermore, they reported significant more frequent co-use of illicit drugs, worse physical well-being, lower treatment satisfaction and more craving experience 4 weeks after the switch compared with the treatment under BUP-SL. Patients 16 weeks under BUP-XR reported significant more illicit co-use and lower treatment satisfaction compared with patients under BUP-SL. Connections between therapy dissatisfaction, physical discomfort, experienced craving and drug co-consumption were discovered. In the first weeks after the medication switch, patients experience potentially distressing symptoms, which, however, seem to diminish over time. Close supervision and comprehensive patient education on possible burdens of the medication switch to the BUP-XR might prevent unfavourable treatment courses and premature therapy dropouts.

The COVID-19 pandemic can be characterized as a chronic stressor affecting the hypothalamic-pituitary-adrenal (HPA) axis, indexed by glucocorticoids (e.g., cortisol). We investigated whether salivary cortisol level is increased during a lockdown and whether a lockdown condition affects the association between loneliness, specific COVID-19 related stressors and salivary cortisol level. We conducted a smartphone-based ecological momentary assessment (EMA) study with 280 participants in Germany who experienced at least mild loneliness and distress amid COVID-19 from August 2020 to March 2021. We measured their momentary loneliness and COVID-related stressors including worries, information seeking behaviors and feelings of restriction during "no-lockdown" or "lockdown" stages amid COVID-19. Their salivary cortisol was measured 4 times on the last day of a 7-day EMA study. We found a significant increase in salivary cortisol levels during lockdown compared to no-lockdown. Lockdown stage was found to moderate the relationship between momentary loneliness and salivary cortisol level, i.e., loneliness was positively related to cortisol level specifically during lockdown. Mechanisms explaining the effect of forced social isolation on the association between loneliness and salivary cortisol need to be investigated in future studies.

BACKGROUND:Animal-assisted intervention has become a common therapeutic practice used for patients with dementia in home-dwelling and institutions. The most established procedure is a visiting service by specially trained dogs and their owners to improve social interactions and reduce symptoms of agitation.OBJECTIVES:The study aims to investigate the effects of a therapy dog on agitation of inpatients with dementia in a gerontopsychiatric ward.MATERIALS AND METHODS:The severity of agitation was assessed by a rater blinded for the presence of the dog via the Overt Agitation Severity Scale (OASS). The scale was conducted on 1 day with the dog and his handler present (resident doctor on the ward) and on another day with only the handler present. Each patient was his/her own control. Heart rate variability (HRV) and serum level of brain-derived neurotrophic factor (BDNF) of the patients were measured on both days. 26 patients with the Mini-Mental Status Examination (MMSE) score <21 and the diagnosis of dementia were included in the study.RESULTS:A significant reduction of agitation in the OASS could be shown when the dog was present (p = 0.006). The data neither demonstrated a difference in the HRV for the parameters mean heart rate (p = 0.65), root mean square of successive differences (p = 0.63), and high frequencies (p = 0.27) nor in serum BDNF concentrations (p = 0.42).DISCUSSION:Therapy dogs can be implemented as a therapeutic tool in a gerontopsychiatric ward to reduce symptoms of agitation in patients with dementia. The study was registered in the German Clinical Trials Register (DRKS00024093).

Abstract Introduction Brain-derived neurotrophic factor (BDNF) has been implicated in the pro-neurogenic effect of selective serotonin reuptake inhibitors. In this study, we used Tph2 −/− mice lacking brain serotonin to dissect the interplay between BDNF and the serotonin system in mediating the effects of antidepressant pharmacotherapy on adult neurogenesis in the hippocampus. Methods Besides citalopram (CIT), we tested tianeptine (TIA), an antidepressant whose mechanism of action is not well understood. Specifically, we examined cell survival and endogenous concentrations of BDNF following daily injection of the drugs. Results Twenty-one days of CIT, but not of TIA, led to a significant increase in the survival of newly generated cells in the dentate gyrus of wild-type mice, without a significant effect on BDNF protein levels by either treatment. In Tph2 −/− mice, adult neurogenesis was consistently increased. Furthermore, Tph2 −/− mice showed increased BDNF protein levels, which were not affected by TIA but were significantly reduced by CIT. Discussion We conclude that the effects of CIT on adult neurogenesis are not explained by changes in BDNF protein concentrations in the hippocampus.

Background: Research on quality of life (QoL) of chronically ill patients provides an opportunity to evaluate the efficacy of long-term treatments. Although it is established that opioid replacement therapy is an effective treatment for opioid-dependent patients, there is little knowledge about physical and psychological functioning of QoL for different treatment options. Objectives: Altogether, 248 opioid-dependent patients receiving substitution treatment with either methadone/levomethadone (n = 126), diamorphine (n = 85), or buprenorphine (n = 37) were recruited in 6 German therapy centers. Methods: Sociodemographic data were collected. QoL – physical and psychological functioning – for different substitutes was assessed using the Profile of the Quality of Life in the Chronically Ill (PLC) questionnaire. Results: Patient groups were similar regarding age and duration of opioid dependence. Employment rate was significantly higher (p < 0.005, φ = 0.22) in the buprenorphine group (46%) compared to methadone (18%). Dosage adjustments were more frequent (p < 0.001, φ = 0.29) in diamorphine (55%) than in methadone (30%) or buprenorphine (19%) patients. Buprenorphine and diamorphine patients rated their physical functioning substantially higher than methadone patients (p < 0.001, η2 = 0.141). Diamorphine patients reported a higher psychological functioning (p < 0.001, η2 = 0.078) and overall life improvement (p < 0.001, η2 = 0.060) compared to methadone, but not compared to buprenorphine patients (both p > 0.25). Conclusion: Measurement of important QoL aspects indicates significant differences for physical and psychological functioning in patients receiving the substitutes methadone/levomethadone, diamorphine, and buprenorphine. This could be relevant for the differential therapy of opioid addiction.

Serotonin (5-hydroxytryptamine, 5-HT) is a crucial signal in the neurogenic niche of the hippocampus, where it is involved in antidepressant action. Here, we utilized a new transgenic rat model (TetO-shTPH2), where brain 5-HT levels can be acutely altered based on doxycycline (Dox)-inducible shRNA-expression. On/off stimulations of 5-HT concentrations might uniquely mirror the clinical course of major depression (e.g., relapse after discontinuation of antidepressants) in humans. Specifically, we measured 5-HT levels, and 5-HT metabolite 5-HIAA, in various brain areas following acute tryptophan hydroxylase 2 (Tph2) knockdown, and replenishment, and examined behavior and proliferation and survival of newly generated cells in the dentate gyrus. We found that decreased 5-HT levels in the prefrontal cortex and raphe nuclei, but not in the hippocampus of TetO-shTPH2 rats, lead to an enduring anxious phenotype. Surprisingly, the reduction in 5-HT synthesis is associated with increased numbers of BrdU-labeled cells in the dentate gyrus. At 3 weeks of Tph2 replenishment, 5-HT levels return to baseline and survival of newly generated cells is unaffected. We speculate that the acutely induced decrease in 5-HT concentrations and increased neurogenesis might represent a compensatory mechanism.

Serum BDNF concentrations in 2053 participants of the Berlin Aging Study II (BASE-II; 1572 individuals from the older age group [60-85 years], 481 individuals from the younger-age reference group [22-37 years]) were studied. There was no effect of age, sex, body mass index, self-reported depression, or BDNF Val66Met variant on serum BDNF concentrations. Multiple linear regression analysis failed to detect significant relationships of Digit Symbol Substitution Test score and Consortium to Establish a Registry for Alzheimer's Disease memory score to BDNF levels. However, we detected a positive correlation between platelet counts and BDNF levels (r = 0.303, p < 0.001). Our findings do not support an effect of aging, self-reported depression, or the Val66Met variant on serum BDNF concentrations. The role of thrombocytes in the biology of serum BDNF merits further study. (c) 2021 Elsevier Inc. All rights reserved.

Background Brain-derived neurotrophic factor (BDNF) exerts its effects on neural plasticity via 2 distinct receptor types, the tyrosine kinase TrkB and the p75 neurotrophin receptor (p75NTR). The latter can promote inflammation and cell death while TrkB is critically involved in plasticity and memory, particularly in the hippocampus. Acute and chronic stress have been associated with suppression of hippocampal BDNF expression and impaired hippocampal plasticity. We hypothesized that p75NTR might be involved in the hippocampal stress response, in particular in stress-induced BDNF suppression, which might be accompanied by increased neuroinflammation. Method We assessed hippocampal BDNF protein concentrations in wild-type mice compared that in mice lacking the long form of the p75NTR (p75NTR (ExIII-/-) ) with or without prior exposure to a 1-hour restraint stress challenge. Hippocampal BDNF concentrations were measured using an optimized ELISA. Furthermore, whole-brain mRNA expression of pro-inflammatory interleukin-6 ( Il6 ) was assessed with RT-PCR. Results Deletion of full-length p75NTR was associated with higher hippocampal BDNF protein concentration in the stress condition, suggesting persistently high hippocampal BDNF levels in p75NTR-deficient mice, even under stress. Stress elicited increased whole-brain Il6 mRNA expression irrespective of genotype; however, p75NTR (ExIII-/-) mice showed elevated baseline Il6 expression and thus a lower relative increase. Conclusions Our results provide evidence for a role of p75NTR signaling in the regulation of hippocampal BDNF levels, particularly under stress. Furthermore, p75NTR signaling modulates baseline but not stress-related Il6 gene expression in mice. Our findings implicate p75NTR signaling as a potential pathomechanism in BDNF-dependent modulation of risk for neuropsychiatric disorders.

Background: Spinal cord injuries (SCI) often lead to devastating loss of neurological functions. Among other therapeutic methods, acupuncture is applied to support recovery. In former studies with healthy volunteers, we demonstrated an acupuncture-induced mobilization of potential neuroprogenitors. We hypothesized that this might also occur in patients with SCI and thereby improve regeneration. Methods: Four patients with SCI were acupunctured 15 times over a period of eight weeks. Before and after each acupuncture, CD133+34– cells were determined as potential neuroprogenitors by flow cytometry. By means of Elisa, we measured matrix metalloproteinase 9 (MMP-9), which is suggested to be involved in the mobilization of progenitor cells, and brain-derived neurotrophic factor (BDNF), a neurotrophin regulating neurogenesis. Patients’ motor and sensory functions were determined by American Spinal Injury Association Impairment Scale (AIS), and the quality of life was assessed using short form (SF)-36. Results: We observed that the number of potential neuroprogenitors increased gradually in peripheral blood over the eight weeks’ course of acupuncture treatment with a concomitant increase of MMP-9 and decrease in BDNF (p<0.05). Patients felt an improved sensory function and showed a positive perception of acupuncture treatment, while no clear changes in motor function were documented. Conclusion: Our results suggest that acupuncture induces the mobilization of potential neuroprogenitors in SCI patients, improvement of subjective sensory function and a better quality of life. Whether and to what extent acupuncture supports regeneration needs to be verified in future studies. Study registration: ISRCTN, ISRCTN71857369, retrospectively registered 18 February 2019, http://www.isrctn.com/ISRCTN71857369).

Animal models in psychiatric research are indispensable for insights into mechanisms of behaviour and mental disorders. Distress is an important aetiological factor in psychiatric diseases, especially depression, and is often used to mimic the human condition. Modern bioethics requires balancing scientific progress with animal welfare concerns. Therefore, scientifically based severity assessment of procedures is a prerequisite for choosing the least compromising paradigm according to the 3Rs principle. Evidence-based severity assessment in psychiatric animal models is scarce, particularly in depression research. Here, we assessed severity in a cognitive depression model by analysing indicators of stress and well-being, including physiological (body weight and corticosterone metabolite concentrations) and behavioural (nesting and burrowing behaviour) parameters. Additionally, a novel approach for objective individualised severity grading was employed using clustering of voluntary wheel running (VWR) behaviour. Exposure to the paradigm evoked a transient elevation of corticosterone, but neither affected body weight, nesting or burrowing behaviour. However, the performance in VWR was impaired after recurrent stress exposure, and the individual severity level increased, indicating that this method is more sensitive in detecting compromised welfare. Interestingly, the direct comparison to a somatic, chemically induced colitis model indicates less distress in the depression model. Further objective severity assessment studies are needed to classify the severity of psychiatric animal models in order to balance validity and welfare, reduce the stress load and thus promote refinement.

Objective Preclinical evidence suggests a role for brain-derived neurotrophic factor (BDNF) in the mode of action of electroconvulsive therapy (ECT). Clinical data regarding BDNF levels in serum or plasma are more inconsistent. We measured BDNF levels from the cerebrospinal fluid (CSF) in patients with major depression before and shortly after a course of ECT. Methods Cerebrospinal fluid and serum BDNF levels were determined using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Results We included 9 patients with a severe depressive episode within a major depressive disorder into the study. The CSF BDNF concentrations at baseline were lower compared with those CSF BDNF levels after the complete ECT treatment (P = 0.042), whereas no such a constellation was found for serum BDNF. No associations between the BDNF levels and the amount of individual ECT sessions or the reduction of the depressive symptoms were found. Conclusions For the first time, it has been shown that CSF BDNF concentrations increase during a course of ECT in patients with a severe unipolar depressive episode, which is in line with the neurotrophin hypothesis as a mode of action of ECT, although it was not possible to demonstrate either a dose-effect relation or a relationship with the actual antidepressant effects in our small sample. Major limitation is the small sample size.

Objective: Depression and coronary heart disease (CHD) are highly comorbid conditions. Brain-derived neurotrophic factor (BDNF) plays an important role in cardiovascular processes. Depressed patients typically show decreased BDNF concentrations. We analysed the relationship between BDNF and depression in a sample of patients with CHD and additionally distinguished between cognitive-affective and somatic depression symptoms. We also investigated whether BDNF was associated with somatic comorbidity burden, acute coronary syndrome (ACS) or congestive heart failure (CHF). Methods: The following variables were assessed for 225 hospitalised patients with CHD: BDNF concentrations, depression [Patient Health Questionnaire-9 (PHQ-9)], somatic comorbidity (Charlson Comorbidity Index), CHF, ACS, platelet count, smoking status and antidepressant treatment. Results: Regression models revealed that BDNF was not associated with severity of depression. Although depressed patients (PHQ-9 score >7) had significantly lower BDNF concentrations compared to non-depressed patients ( p = 0.04), this was not statistically significant after controlling for confounders ( p = 0.15). Cognitive-affective symptoms and somatic comorbidity burden each closely missed a statistically significant association with BDNF concentrations ( p = 0.08, p = 0.06, respectively). BDNF was reduced in patients with CHF ( p = 0.02). There was no covariate-adjusted, significant association between BDNF and ACS. Conclusion: Serum BDNF concentrations are associated with cardiovascular dysfunction. Somatic comorbidities should be considered when investigating the relationship between depression and BDNF.

Diamorphine was first legalized as a novel treatment option for heroin dependence in Germany in 2009. Today, specialized clinics in ten German cities provide diamorphine to heavily addicted patients. As the medical and societal context of diamorphine-assisted therapy is evolving, continued research into patients' perceptions of opioid replacement therapy remains important. From February 2018 to June 2018, we conducted a survey study of outpatients on maintenance treatment with either diamorphine (n = 85) or methadone/levomethadone (n = 126). Patients were asked to complete a self-report questionnaire querying, besides socio-demographic information, the study participant's satisfaction with the substitute drug, relapse with illicit drugs, patterns of craving, and alcohol consumption. Duration of opioid dependence did not differ significantly between groups. Patients on diamorphine were approximately 3 years younger than patients on methadone/levomethadone. They also had a higher frequency of daily intake of their substitute drug and had had their dosage adjusted more often during the preceding 6 months. Still, diamorphine patients reported greater satisfaction with their substitute drug in tandem with significant reductions in relapse-related behaviors and cravings. While the most common relapse reported by patients on methadone replacement was heroin relapse (68%), most instances of illicit drug use in the diamorphine group involved cocaine (48%). Although self-reported alcohol consumption did not differ significantly between groups, a higher percentage of diamorphine patients than methadone patients endorsed decreased alcohol consumption since entering therapy. Taken together, these findings point to meaningful differences between diamorphine and methadone/levomethadone in opioid replacement therapy.

Aims Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis has been reported to be affected in alcohol use disorder (AUD). It has been suggested that pharmacological relapse prevention in AUD might exert its effects partly by modulation of HPA axis activity. Here, we assessed the effects of high-dose treatment with baclofen on HPA axis activity in alcohol-dependent patients within a 24-week randomized, placebo-controlled trial (BACLAD study). Methods Plasma levels of copeptin, adrenocorticotropic hormone (ACTH), and cortisol were measured at 3 timepoints in alcohol-dependent patients during the study. Corresponding plasma levels in healthy controls were assessed once. Results ACTH blood levels were significantly higher in the group of alcohol-dependent patients compared to controls. In patients receiving individually titrated high-dose baclofen, plasma cortisol levels decreased significantly, whereas no significant alterations were found in the placebo group. Conclusions Our study underlines again the role of HPA axis alterations in AUD. Furthermore, a decrease in hormonal stress levels during treatment with high-dose baclofen might contribute to the relapse preventive effects of this compound.