Neuropsychopharmacology Reports最新文献

Background: An innovative New South Wales government funded statewide Cannabis Medicines Advisory Service (CMAS) operated between January 2018 and June 2022. The service provided comprehensive patient-specific and evidence-based information to support health professionals in prescribing and patient care decisions. This study aimed to describe real-world data collected by CMAS.

Methods: A sub-set of de-identified, patient-specific enquiries collected between January 2021 and June 2022 (n = 123/567; 21.7%) were analyzed using R version 4.2.1. Diagnosis, indication, and comorbidities were coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology.

Results: Most patient-specific enquiries from medical practitioners were from general practitioners (n = 103/123; 83.7%). Female (n = 53/123; 43.1%) and male (n = 59/123; 48.0%) patients were similarly represented. Sex was not specified for 8.9% (n = 11/123) of patients. The mean age of patients was 52.1 years (range <10-90). The most common three diagnoses were osteoarthritis, anxiety, and chronic pain. Indications that were most frequently reported included chronic pain, anxiety, back pain, non-neuropathic pain, and insomnia. Comedications were most commonly non-opioid and opioid analgesics and antidepressants. Most practitioners were considering prescribing a cannabidiol (CBD) product for their patient. Cannabinoid composition selection guidance provided by CMAS was predominantly (delta-9-tetrahydrocannabinol) THC:CBD ~1:1, followed by CBD-only products. CMAS was contacted by health professionals regarding the management of potential adverse events for five patients.

Conclusion: The findings of this study shed light on the information medical practitioners were seeking to inform their clinical decision-making about medical cannabis and can inform the development of clinical guidance resources.

Aim: Psychopharmacotherapy plays an important role in the treatment of mentally disordered offenders (MDOs) with schizophrenia spectrum disorders. However, there have been few large-scale reports from multiple forensic psychiatric wards. This study aimed to clarify the current state of antipsychotic medications for MDOs with schizophrenia spectrum disorders in Japanese forensic psychiatric wards.

Methods: Medical information, including age, sex, psychiatric diagnosis, index offense, seclusion or restraint experience during hospitalization, and medication for patients discharged from 32 forensic wards nationwide between September 1, 2019 and December 31, 2021 was provided by the Database Scientific Utilization Project of Japanese forensic psychiatric wards. We analyzed the data of MDOs with schizophrenia spectrum disorders who were prescribed psychotropic medications at the time of discharge, especially focusing on comparing differences between the three groups (clozapine, long-acting injection (LAI), and other medications).

Results: A total of 362 MDOs with schizophrenia spectrum disorders were prescribed psychotropic medications at discharge. The prescription rates of clozapine and LAI were 23.2% and 24.9%, respectively. Additionally, the rate of antipsychotic polypharmacy was 37.8%. Among the three groups, the clozapine group had the highest rate of seclusion experience (46.4%), a long mean length of hospitalization (1758 days), and the lowest rate of antipsychotic polypharmacy (4.8%). Olanzapine was the most commonly prescribed antipsychotic medication.

Conclusion: This study revealed the current state of antipsychotic medications for MDOs admitted to forensic psychiatric wards in Japan. Future studies are needed to clarify the relevance of antipsychotic medications in the prognosis of MDOs.

Aim: Selective serotonin reuptake inhibitors are thought to exert a clinical effect through various mechanisms, including through alteration in synaptic plasticity. Repetitive transcranial magnetic stimulation can induce temporary changes in synaptic excitability in cerebral cortex that resemble long-term potentiation and long-term depression that serve as a measure of synaptic plasticity in vivo. A version of repetitive transcranial magnetic stimulation called continuous theta burst stimulation can induce inhibition of cortical excitability that can be measured through a motor evoked potential. Previous work has suggested that this response can be modulated by administration of selective serotonin reuptake inhibitors.

Method: Thirty-one healthy volunteers received both fluoxetine 20 mg and placebo in randomly ordered sessions, followed by spaced continuous theta burst stimulation to motor cortex. Changes in Motor Evoked Potentials were then recorded over 60 min.

Results: The response to spaced continuous theta burst stimulation did not differ significantly between fluoxetine and placebo sessions. Spaced continuous theta burst stimulation produced a paradoxical excitatory response in an unexpected number of participants.

Conclusion: A single dose of fluoxetine 20 mg does not influence the response to continuous theta burst stimulation. Previous results suggesting an effect of selective serotonin reuptake inhibitors on inhibitory non-invasive brain stimulation protocols may be due to insufficiently large sample sizes.

Aim: This study aimed to elucidate the effects of repetitive transcranial magnetic stimulation (rTMS) on weight, body mass index (BMI), and lipid metabolism in patients with treatment-resistant depression (TRD).

Methods: This retrospective observational study included patients with TRD who received rTMS treatment at the Jikei University Hospital from September 2018 to August 2021. The patients were diagnosed based on the DSM-5 and ICD-10 criteria and treated using the NeuroStar TMS System. For 3-6 weeks, 10-Hz rTMS was administered to the left dorsolateral prefrontal cortex at 120% motor threshold. The primary outcomes were changes in weight and BMI, whereas the secondary outcomes included changes in total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels, thyroid function indicators, as well as HAMD-17, HAMD-24, and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Statistical analysis was conducted using paired t-tests and repeated measures ANOVA.

Results: Among the 34 patients (20 men and 14 women) included, no significant changes were observed in weight or BMI after rTMS treatment (average weight reduction: -0.50 kg, 95% CI: -0.14 to 0.56, p = 0.24; average BMI reduction: -0.21, 95% CI: -0.10 to 0.61, p = 0.15). However, significant reductions in total, HDL, and LDL cholesterol levels and FT4 were observed. Furthermore, the HAMD-17, HAMD-24, and MADRS scores significantly increased post-treatment.

Conclusion: rTMS treatment did not affect weight or BMI in patients with TRD but is believed to improve lipid metabolism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Some children with ASD show enhanced cortisol response to stress. BTBR T⁺ Itpr3^tf/J (BTBR) mice, an ASD model, display behavior consistent with the three diagnostic categories of ASD and exhibit an exaggerated response to stress in adulthood. However, it remains unclear how basal corticosterone levels change and how the hypothalamic-pituitary-adrenal axis responds to stress during the early life stages in BTBR mice. In this study, we found that basal corticosterone levels showed characteristic changes, peaking at weaning during postnatal development in both BTBR and control C57BL/6J (B6J) mice. Furthermore, we observed higher corticosterone and corticotropin-releasing hormone levels in BTBR mice than in B6J mice following acute stress exposure during weaning; however, adrenocorticotropic hormone levels were lower in BTBR mice. Glucocorticoid receptor mRNA expression levels in the hippocampus and lateral septum after stress were higher in BTBR mice than in B6J mice. This study documented changes in corticosterone levels at baseline during postnatal development in mice and showed that BTBR mice exhibited disrupted stress responses at weaning.

Aim: Although numerous studies have reported that chronic alcohol consumption causes brain volume reduction and cerebrospinal fluid volume increase, few studies have examined the acute effects of alcohol on brain structure. This study aims to investigate the short-term brain volume changes following alcohol administration.

Methods: Moderate doses of alcohol were administered intravenously to 18 healthy volunteers for a total of 90 min to achieve a blood alcohol concentration of 0.5 mg/mL. An alcohol clamp method combined with physiologically based pharmacokinetic modeling was used to achieve fine control over blood alcohol concentration. T1 images with 3T MRI were scanned at three time points: baseline, 0 min, and 90 min after the end of alcohol administration. Cortical, subcortical, and ventricular volumes were computed after segmentation with FreeSurfer. Repeated measures analysis of variance was used to evaluate longitudinal changes in brain volume at 96 regions.

Results: Acute alcohol administration increased bilateral lateral ventricular volumes, which lasted until 90 min after the end of alcohol injection. On the other hand, the volumes of total gray matter, left precentral cortex, left caudal middle frontal cortex, and left superior frontal cortex decreased after alcohol administration, but these changes disappeared 90 min after the end of alcohol administration.

Conclusion: Acute injection of moderate doses of alcohol may enlarge ventricle volumes and reduce gray matter volumes. The transient volume changes caused by acute administration of alcohol may be related to changes in CSF flow and water content of brain tissue, which warrants further study.

Aim: Individuals with insomnia frequently have comorbid depression or anxiety. This study sought to provide a preliminary indication of the effects of lemborexant (LEM) in subjects treated for mild depression/anxiety symptoms.

Methods: E2006-G000-303 (NCT02952820; EudraCT 2015-001463-39; SUNRISE-2) was a 12-month, phase 3, randomized, placebo-controlled, double-blind study where subjects with insomnia disorder were randomized (1:1:1) to placebo, LEM 5 mg (LEM5), or LEM 10 mg (LEM10) for 6 months. During the second 6 months (not reported), placebo-treated subjects were re-randomized to LEM5 or LEM10. In this post hoc analysis, changes from baseline (CFB) in subject-reported (subjective) sleep onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), total sleep time (sTST), Fatigue Severity Scale, and Insomnia Severity Index were evaluated in subjects treated with medications for symptoms of depression/anxiety (subpopulation).

Results: Of 949 randomized subjects, 61 treated with medications for symptoms of depression/anxiety were included. In the subpopulation, CFB comparing LEM with placebo were generally smaller than the overall population due to a larger placebo response in the subpopulation. However, the magnitudes of CFB within the active treatment groups for sSOL, sWASO, sTST, and sSE were similar between the subpopulation and the overall population. No new safety signals were observed in the subpopulation.

Conclusion: LEM treatment benefited subjects with insomnia treated with medications for depression/anxiety symptoms, with no new safety signals. A greater placebo response in the subpopulation than in the overall population decreased the drug versus placebo effect size for LEM, as has been reported for other insomnia medications.

3,4-methylenedioxymethamphetamine (MDMA), a commonly abused recreational drug, induces prosocial effects such as increased sociability and empathy. The nucleus accumbens (NAc) has been suggested to play a crucial role in these MDMA-mediated prosocial effects. However, the relationship between social behavior and NAc neural activity, and the effects of MDMA on this relationship, remain unknown. In this study, we measured NAc neural activity using fiber photometry and classified the behaviors of mice at times of transient increases in NAc neural activity during the social approach test (SAT). We found that NAc neural activity transiently increased at the onset of turning toward and sniffing novel mice during the SAT, although the frequency of turning was relatively low. We then examined the effects of MDMA on behavior and NAc neural activity and found that MDMA decreased the duration of sniffing per bout but did not alter NAc neural activity at the onset of turning toward or sniffing novel mice. These results suggest that MDMA does not affect the transient increase in NAc neural activity at the onset of social behaviors.

Patients with epilepsy often require long-term treatment with antiseizure medications, and their impact on daily activities, particularly driving, is of significant concern. The recently published "Guideline for Evaluating Effects of Psychotropic Drugs on the Performance to Drive a Motor Vehicle" in Japan provides a framework that can be referred to for not only the evaluation of new drugs but also the reevaluation of approved drugs. This study conducted a literature review regarding the effects of carbamazepine, valproate, lamotrigine, lacosamide, and levetiracetam, which are frequently prescribed for epilepsy, on driving performance following the guideline's tiered evaluation approach. Analyses of pharmacological, pharmacodynamic, and adverse events suggested that these drugs primarily affect arousal function. Driving studies showed that acute administration of carbamazepine, but not chronic monotherapy with carbamazepine, valproate, lamotrigine, and levetiracetam, significantly impairs driving performance. Epidemiological studies have not identified a definitive association between these drugs and traffic accidents. Initial administration of these five antiseizure medications may affect driving performance, warranting special attention, but the influence appears to diminish with continued use. Nevertheless, while long-term administration of these five drugs may not have a clinically meaningful effect on driving performance, safe driving is not guaranteed for each individual patient, and appropriate individualized guidance is important in clinical practice.

Background: While drugs are sometimes taken during deliberate self-harm (DSH), no study has attempted to analyze drugs in the blood of DSH patients and compare them with prescribed medications or other drugs. In this study, drugs were analyzed from the blood of DSH patients, and the detected, prescribed, and suspected drugs were documented.

Methods: Patients who practiced DSH and were transferred to the emergency sites of Fukuoka University Hospital between April 2021 and September 2022 participated in the study. Psychiatrists assessed information such as the history of psychiatric treatment and recent methods of DSH, as well as prescribed drugs within 1 month of presenting to the hospital. Blood samples were analyzed using LC-MS/MS. Participants were divided into groups according to whether or not they were prescribed psychotropics within 1 month.

Results: Fifty-five patients were enrolled in the study. Forty had been prescribed psychotropics within 1 month of hospital admission. However, non-prescribed drugs (NPD) were detected in 42 of the 55 participants (76%). The detection of NPD was significantly high among patients with overdose of medications and OTC drugs (p = 0.036), but NPD were also detected in patients who engaged in other methods (n = 14), and in patients without prescribed medication (n = 10).

Discussion: This is the first study focused on the drug analysis of blood from patients engaging in DSH. Approximately 80% of the DSH patients in this study had taken NPD, revealing a large discrepancy between prescribed medications and those detected in the blood.