Psychopharmacology最新文献

{"title":"Optimizing esketamine administration for postoperative depression: a comprehensive study on laparoscopic bariatric surgery patients.","authors":"Jiabao Dai, Yanfeng Lu, Zhiqing Zou, Zhouquan Wu","doi":"10.1007/s00213-024-06673-y","DOIUrl":"https://doi.org/10.1007/s00213-024-06673-y","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have reported conflicting findings regarding the efficacy of esketamine in managing postoperative depression. While the positive effects of subanesthetic doses esketamine have been observed in treatment-resistant depression, the response to this medication in patients experiencing depression following surgery has not been consistent. Building upon the known impact of anesthesia on brain function, we have formulated a hypothesis suggesting that the timing of esketamine administration in relation to anesthesia may significantly affect its efficacy in managing postoperative depression. The aim of this study was to investigate the effect of esketamine administered at different time points before and after anesthesia.</p><p><strong>Methods: </strong>Our randomized, double-blind, controlled study involved 120 patients undergoing laparoscopic bariatric surgery, randomly divided into three groups. Group Post- ESK received an intravenous injection of esketamine at a dose of 0.2 mg/kg after anesthesia induction. Group Pre- ESK received the same esketamine dosage 2 h prior to anesthesia induction. Group Placebo served as the control group and received a 0.9% saline solution after induction. The primary outcome measures of the study were depression scores as measured by Patient Health Questionnaire-9 (PHQ-9) and plasma brain-derived neurotrophic factor (BDNF) levels.</p><p><strong>Results: </strong>On the first postoperative day, the PHQ-9 scores, incidence and severity of postoperative depression in the Pre-ESK group were significantly lower than those in the Post-ESK and placebo groups (P < 0.05). Additionally, plasma BDNF levels in the Pre-ESK group were significantly higher than those in the Post-ESK and placebo groups (P < 0.05). Notably, there was a negative correlation between PHQ-9 scores and plasma BDNF levels.</p><p><strong>Conclusions: </strong>Our study supports the potential for subanesthetic dose esketamine to alleviate postoperative depression symptoms following laparoscopic bariatric surgery, and anesthetic drugs have a significant effect on its efficacy. The use of subanesthetic dose esketamine after anesthesia does not improve postoperative depression symptoms in patients undergoing laparoscopic bariatric surgery, while the use of sub-anesthetic dose esketamine before anesthesia can improve postoperative depression symptoms.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prefrontal cortex-nucleus reuniens-hippocampus network exhibits sex-differentiated responses to stress and antidepressant treatment in rats.","authors":"V Kafetzopoulos, N Kokras, Filippos Katsaitis, N Sousa, H Leite-Almeida, I Sotiropoulos, C Dalla","doi":"10.1007/s00213-024-06667-w","DOIUrl":"https://doi.org/10.1007/s00213-024-06667-w","url":null,"abstract":"<p><strong>Rationale: </strong>Depression is a serious psychiatric disease, which is diagnosed twice as frequently in women than men. We have recently shown that lesioning or inactivation of the nucleus reuniens (RE), which interconnects the prefrontal cortex (PFC) and hippocampus, promoted resilience to stress in males, exerts an antidepressant effect in the Forced Swim Test (FST) and prevents the development of behavioral and neurobiological alterations induced by the chronic mild stress model of depression.</p><p><strong>Objectives: </strong>In this study, we expand our findings on the FST in female rats and we investigate whether RE lesion presents sex differences following treatment with two distinct antidepressants, a selective serotonin reuptake inhibitor, i.e. sertraline and a tricyclic antidepressant, i.e. clomipramine.</p><p><strong>Methods: </strong>Male and female rats received either a surgical lesion of the RE or sham operation, then treated with vehicle, sertraline (10mg/kg) or clomipramine (10mg/kg) and were subjected to the FST. Activation of key brain areas of interest (PFC, Hippocampus and RE) were measured by c-Fos immunoreactivity.</p><p><strong>Results: </strong>RE lesion induced an antidepressant-like phenotype in both female and male rats, confirming its crucial role in the stress response. Similarly to RE lesion, sertraline treatment resulted in increased swimming and decreased immobility duration, as well as enhanced head shake frequency, in both sexes. Notably, climbing behavior was increased only following clomipramine treatment. RE area was less active in females compared to male rats and in clomipramine-treated males compared to their corresponding vehicle-group. Activation of the PFC and the CA1 hippocampal area was reduced in clomipramine-treated females, in comparison to vehicle-treated female rats. This effect was not evident in males, which exhibited less activation in the PFC and the hippocampus than females.</p><p><strong>Conclusion: </strong>Re lesion proves equally effective in female and male rats, but sex is highlighted as a pivotal factor in behavioral and treatment response in FST, as well as in related circuit connectivity and activation.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol enhances socially transmitted food preference: a role of acetylcholine in the mouse basal forebrain.","authors":"Chih-Yu Chang, Wen Dai, Sherry Shu-Jung Hu","doi":"10.1007/s00213-024-06670-1","DOIUrl":"https://doi.org/10.1007/s00213-024-06670-1","url":null,"abstract":"<p><strong>Rationale and objective: </strong>Rodents acquire food information from their conspecifics and display a preference for the conspecifics' consumed food. This social learning of food information from others promotes the survival of a species, and it is introduced as the socially transmitted food preference (STFP) task. The cholinergic system in the basal forebrain plays a role in the acquisition of STFP. Cannabidiol (CBD), one of the most abundant phytocannabinoids, exerts its therapeutic potential for cognitive deficits through versatile mechanisms of action, including its interaction with the cholinergic system. We hypothesize a positive relationship between CBD and STFP because acetylcholine (ACh) is involved in STFP, and CBD increases the ACh levels in the basal forebrain.</p><p><strong>Materials and methods: </strong>Male C57BL/6J mice were trained to acquire the STFP task. We examined whether CBD affects STFP memory by administering CBD (20 mg/kg, i.p.) before the STFP social training. The involvement of cholinergic system in CBD's effect on STFP was examined by knockdown of brain acetylcholinesterase (AChE), applying a nonselective muscarinic antagonist SCO (3 mg/kg, i.p.) before CBD treatment, and measuring the basal forebrain ACh levels in the CBD-treated mice.</p><p><strong>Results: </strong>We first showed that CBD enhanced STFP memory. Knockdown of brain AChE also enhanced STFP memory, which mimicked CBD's effect on STFP. SCO blocked CBD's memory-enhancing effect on STFP. Our most significant finding is that the basal forebrain ACh levels in the CBD-treated mice, but not their control counterparts, were positively correlated with mice's STFP memory performance.</p><p><strong>Conclusion: </strong>This study indicates that CBD enhances STFP memory in mice. Specifically, those which respond to CBD by increasing the muscarinic-mediated ACh signaling perform better in their STFP memory.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of nightly use of 150 mg cannabidiol on daytime neurocognitive performance in primary insomnia: a randomized controlled pilot trial.","authors":"Andrea J Narayan, Amie C Hayley, Sarah Rose, Lauren Di Natale, Luke A Downey","doi":"10.1007/s00213-024-06674-x","DOIUrl":"https://doi.org/10.1007/s00213-024-06674-x","url":null,"abstract":"<p><strong>Rationale: </strong>Cannabidiol (CBD) is increasingly used as a sleep aid for insomnia; yet neurocognitive and subjective state effects following daily therapeutic use are unclear.</p><p><strong>Objectives: </strong>To measure the effect of daily CBD use on neurocognitive performance and daily subjective mood in a population with primary insomnia.</p><p><strong>Methods: </strong>This study used a randomized, placebo-controlled, parallel design incorporating a single-blind placebo run-in week followed by a two-week double-blind dosing period, during which participants consumed 150 mg CBD (N = 15) or placebo (N = 15) sublingually 60-minutes daily before bed. Attention, executive function, reasoning, information processing, working and episodic memory were assessed using the CogPro system at the beginning of the placebo run-in, after 1-week and 2-weeks of dosing. Subjective states using visual analogue scales and side effects were recorded daily.</p><p><strong>Results: </strong>Cognitive performance was unaffected by nightly CBD supplementation (all p > 0.05). From baseline to trial conclusion, those receiving CBD reported greater experience of calmness, clear-headedness, coordination and were more likely to report side-effects of dry mouth relative to placebo (all p < 0.05).</p><p><strong>Conclusions: </strong>Relative to placebo, daytime cognitive functioning following nightly supplementation as a therapeutic aid for primary insomnia was preserved under trial conditions. Results suggested an overall favourable safety profile, with larger controlled trials and thorough analyses of varying insomnia phenotypes necessary to corroborate these findings.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated exposure to novelty promotes resilience against the amyloid-beta effect through dopaminergic stimulation.","authors":"Cintia Velázquez-Delgado, Eduardo Hernández-Ortiz, Lucia Landa-Navarro, Miguel Tapia-Rodríguez, Perla Moreno-Castilla, Federico Bermúdez-Rattoni","doi":"10.1007/s00213-024-06650-5","DOIUrl":"https://doi.org/10.1007/s00213-024-06650-5","url":null,"abstract":"<p><strong>Rationale: </strong>The accumulation of beta-amyloid peptide (Aβ) in the forebrain leads to cognitive dysfunction and neurodegeneration in Alzheimer's disease. Studies have shown that individuals with a consistently cognitively active lifestyle are less vulnerable to Aβ toxicity. Recent research has demonstrated that intrahippocampal Aβ can impact catecholaminergic release and spatial memory. Interestingly, exposure to novelty stimuli has been found to stimulate the release of catecholamines in the hippocampus. However, it remains uncertain whether repeated enhancing catecholamine activity can effectively alleviate cognitive impairment in individuals with Alzheimer's disease.</p><p><strong>Objectives: </strong>Our primary aim was to investigate whether repeated exposure to novelty could enable cognitive resilience against Aβ. This protection could be achieved by modulating catecholaminergic activity within the hippocampus.</p><p><strong>Methods: </strong>To investigate this hypothesis, we subjected mice to three different conditions-standard housing (SH), repeated novelty (Nov), or daily social interaction (Soc) for one month. We then infused saline solution (SS) or Aβ (Aβ_1-42) oligomers intrahippocampally and measured spatial memory retrieval in a Morris Water Maze (MWM). Stereological analysis and extracellular baseline dopamine levels using in vivo microdialysis were assessed in independent groups of mice.</p><p><strong>Results: </strong>The mice that received Aβ_1-42 intrahippocampal infusions and remained in SH or Soc conditions showed impaired spatial memory retrieval. In contrast, animals subjected to the Nov protocol demonstrated remarkable resilience, showing strong spatial memory expression even after Aβ_1-42 intrahippocampal infusion. The stereological analysis indicated that the Aβ_1-42 infusion reduced the tyrosine hydroxylase axonal length in SH or Soc mice compared to the Nov group. Accordingly, the hippocampal extracellular dopamine levels increased significantly in the Nov groups.</p><p><strong>Conclusions: </strong>These compelling results demonstrate the potential for repeated novelty exposure to strengthen the dopaminergic system and mitigate the toxic effects of Aβ_1-42. They also highlight new and promising therapeutic avenues for treating and preventing AD, especially in its early stages.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute analgesic effect of nicotine vaping using three experimental pain induction tasks: a randomized, placebo-controlled laboratory study.","authors":"Michael P Bremmer, Michael B Paladino, Alana M Campbell, Kai Xia, Robert Tarran, Christian S Hendershot, Susan S Girdler","doi":"10.1007/s00213-024-06669-8","DOIUrl":"https://doi.org/10.1007/s00213-024-06669-8","url":null,"abstract":"<p><strong>Rationale: </strong>Pain and nicotine use are co-occurring conditions with a significant impact on health. Experimental evidence supports an acute analgesic effect of nicotine which may reinforce nicotine use among those with chronic pain. Evidence for nicotine analgesia have primarily been gathered in combustible cigarette users and have not been extended to electronic nicotine delivery systems (ENDS or vaping). Furthermore, the mechanisms of nicotine analgesia in humans are not well understood.</p><p><strong>Objectives: </strong>Assess the effect of acute vaped nicotine on subjective and behavioral indices of pain sensitivity using three tasks designed to probe distinct mechanisms of analgesia.</p><p><strong>Methods: </strong>This study recruited ENDS users (N = 86) to undergo a paced vaping protocol followed by pain tasks in counterbalanced order. Across four sessions, participants vaped e-liquid containing nicotine or placebo, and flavor or no-flavor in a 2 × 2 within-subject design. Assessments included cold pressor, submaximal effort tourniquet to induce ischemic pain, and temporal summation of heat pain, an index of central sensitization.</p><p><strong>Results: </strong>Compared to placebo, nicotine increased cold pressor pain tolerance (η_p² = 0.031), ischemic pain threshold (η_p² = 0.073) and tolerance (η_p² = 0.056) but had no effect on temporal summation of pain. Flavor did not affect pain sensitivity. Females reported greater ischemic pain sensitivity (η_p² = 0.027) and greater reductions in craving (η_p² = 0.086).</p><p><strong>Conclusions: </strong>Consistent with research from tobacco smoking, analgesia may be reinforcing and contribute to nicotine dependence among ENDS users. More research on sex differences is warranted.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isobutyryl-carfentanyl has strong acute toxicity and analgesic effects with high addiction potential.","authors":"Deli Xu, Lixin Kuai, Yuanyuan Chen, Xianbin Zeng, Dan Wang, Bin Di, Peng Xu","doi":"10.1007/s00213-024-06664-z","DOIUrl":"https://doi.org/10.1007/s00213-024-06664-z","url":null,"abstract":"<p><strong>Rationale: </strong>Isobutyryl-carfentanyl is the most recently discovered fentanyl analogue with a chemical structure that is similar to that of carfentanyl. Its analogue, carfentanyl, is regarded as one of the most lethal drugs in the world, with a potency of 10,000 times that of morphine. Therefore, isobutyryl-carfentanyl may possess a comparably high potency and its harmful effects cannot be ignored.</p><p><strong>Objectives: </strong>This study was designed to assess the analgesic effect of isobutyryl-carfentanyl and the potential risks associated with its misuse.</p><p><strong>Methods: </strong>In this study, we assessed the acute toxicity of isobutyryl-carfentanyl by up-and-down-procedure, the analgesic efficacy by hot-plate test, the abuse potential by conditioned place preference (CPP), drug self-administration, and drug discrimination tests, and compared it with fentanyl and carfentanyl.</p><p><strong>Results: </strong>The estimated median lethal dose (LD₅₀) of isobutyryl-carfentanyl administered were 175 mg/kg (intragastric administration, IG), 15.84 mg/kg (intraperitoneal injection, IP), 15.84 mg/kg (subcutaneous injection, SC), and 1.6 mg/kg (intravenous injection, IV), respectively. The 50% maximal analgesic effect (ED₅₀) of isobutyryl-carfentanyl was determined to be 0.00319 mg/kg, with an analgesic potency 14 times that of fentanyl and 0.82 times that of carfentanyl. Isobutyryl-carfentanyl exhibited a significant positional preference at a minimum dose of 0.1 mg/kg, while fentanyl exhibited a significant positional preference at a minimum dose of 0.3 mg/kg. In the heroin (0.05 mg/kg/infusion) self-administration substitution experiment, isobutyryl-carfentanyl showed significant self-administration behaviour at doses of 0.0005-0.001 mg/kg/infusion, with the maximum number of infusions observed at a dose of 0.001 mg/kg. In the heroin (1 mg/kg) drug discrimination experiment, fentanyl (0.005-0.02 mg/kg), carfentanyl (0.0005-0.002 mg/kg), and isobutyryl-carfentanyl (0.001-0.005 mg/kg) were tested in the dose-effect curves. The results showed that all three drugs exhibit dose-dependent increase in the number of drug-associated nose pokes responses and reduction in the rate of nose pokes. The subjective effect potency of isobutyryl-carfentanyl was found to be 4.4 times that of fentanyl and 0.5 times that of carfentanyl.</p><p><strong>Conclusions: </strong>In summary, isobutyryl-carfentanyl has high acute toxicity and analgesic effect, with strong psychological dependence approximately 5 times that of fentanyl and 0.5 times that of carfentanyl, and has extremely high abuse potency.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of low doses of mirtazapine plus venlafaxine produces antidepressant-like effects in rats, without affecting male or female sexual behavior.","authors":"Adriana Álvarez-Silva, Gabriela Rodríguez-Manzo, Rebeca Reyes, Alonso Fernández-Guasti","doi":"10.1007/s00213-024-06661-2","DOIUrl":"https://doi.org/10.1007/s00213-024-06661-2","url":null,"abstract":"<p><strong>Rationale: </strong>Pharmacological treatments for depression are not always effective and produce unwanted side effects. Male and female sexual dysfunction is one of these side effects, which can lead to treatment withdrawal. Combination of two antidepressants with different mechanisms of action, like mirtazapine (MTZ) and venlafaxine (VLF) have been shown to be effective for treatment-resistant depression in humans. Combination of low doses of these drugs may still exert antidepressant-like effects without altering sexual behavior.</p><p><strong>Objectives: </strong>To investigate the potential antidepressant-like effect of the chronic administration of low doses of MTZ plus VLF combined, as well as its impact on male and female sexual behavior in rats.</p><p><strong>Methods: </strong>The antidepressant-like effect of a 14-day treatment with combinations of MTZ plus VLF (0/0, 2.5/3.75 or 5/7.5 mg/kg) was assessed in young adult male and female rats in the forced swim test (FST). The 5/7.5 mg/kg MTZ/VLF combination was also tested in the chronic mild stress (CMS) test, in both males and females treated for 21 days. The sexual effects of this last treatment were assessed in sexually experienced males and in gonadally-intact females during proestrus.</p><p><strong>Results: </strong>The 5/7.5 mg/kg MTZ/VLF combination produced an antidepressant-like effect in the FST and reversed the CMS-induced anhedonia in both male and female rats. This combination did not alter male sexual behavior, female proceptive and receptive behaviors or the regularity of the estrous cycle.</p><p><strong>Conclusion: </strong>The combination of low doses of MTZ and VLF might be a promising therapeutic alternative to treat depression without affecting the sexual response.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of clozapine once-daily versus multiple-daily dosing regimen on relapse in patients with treatment-resistant schizophrenia: A 1-year retrospective cohort study.","authors":"Masaru Tsukahara, Ryuhei So, Kohei Kitagawa, Yuji Yada, Masafumi Kodama, Shinichiro Nakajima, Yoshiki Kishi, Norihito Yamada, Hiroyoshi Takeuchi","doi":"10.1007/s00213-024-06658-x","DOIUrl":"https://doi.org/10.1007/s00213-024-06658-x","url":null,"abstract":"<p><strong>Rationale: </strong>Clozapine, the standard treatment for treatment-resistant schizophrenia (TRS), is generally recommended in a multiple-daily dosing regimen. However, it is commonly administered once daily in clinical practice. Few studies have compared the longitudinal clinical outcomes of these two dosing regimens.</p><p><strong>Objective: </strong>To investigate the effect of once-daily versus multiple-daily dosing regimens of clozapine on relapse in patients with TRS.</p><p><strong>Methods: </strong>This retrospective cohort study included patients with TRS who commenced treatment with clozapine during hospitalization and were discharged between April 2012 and January 2022 from a tertiary psychiatric hospital in Japan. Relapse, defined as a psychiatric exacerbation requiring re-hospitalization within the first-year post-discharge, was analyzed. Multivariable Cox proportional hazards regression analysis compared the relapse risk between once-daily and multiple-daily dosing regimens. A subgroup analysis was conducted to examine the potential interactions between dosing regimen and dose category (low versus high dose).</p><p><strong>Results: </strong>Among 179 patients, 107 (59.8%) received clozapine once daily. No significant difference in the relapse risk was observed between once-daily and multiple-daily dosing regimens (adjusted hazard ratio [aHR]: 1.16; 95% confidence interval [CI]: 0.68-1.99; p = 0.58). However, in patients receiving high doses of clozapine (> 300 mg/day), multiple-daily dosing increased the relapse risk compared to once-daily dosing (aHR: 2.23; 95% CI: 1.00-4.97; p = 0.049).</p><p><strong>Conclusions: </strong>Once-daily clozapine dosing may not be associated with an increased relapse risk. The increased relapse risk in high-dose multiple-daily dosing may be confounded by unmeasured non-adherence. Further randomized controlled trials are required to validate these findings.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of N-acetyl cysteine on intrinsic functional connectivity and neural alcohol cue reactivity in treatment-seeking individuals with alcohol use disorder: a preliminary study.","authors":"Warren B Logge, Paul S Haber, Tristan P Hurzeler, Ellen E Towers, Kirsten C Morley","doi":"10.1007/s00213-024-06656-z","DOIUrl":"https://doi.org/10.1007/s00213-024-06656-z","url":null,"abstract":"<p><p>N-acetyl cysteine (NAC) is a potential pharmacotherapy for alcohol use disorder (AUD), but it is not known whether it modulates neural activation to alcohol cues or intrinsic functional connectivity. We investigated whether NAC attenuates (i) alcohol cue-elicited activation, and (ii) intrinsic functional connectivity compared to placebo in patients with AUD. In this preliminary study, twenty-three individuals (7 females) with moderate-severe AUD received daily NAC (2400 mg/day, n = 9), or a placebo (n = 14) for at least 2 weeks. Participants completed a pre-treatment functional magnetic resonance imaging session (T0) and a post-treatment session (T1) comprising resting-state and visual alcohol cue reactivity task acquisitions. Activation differences between sessions, treatment, and session-by-treatment interaction were assessed. Resting-state functional connectivity examined using 377 node ROI-to-ROIs evaluated whether NAC reduced intrinsic functional connectivity after treatment. There were no differences in alcohol cue reactivity for brain activation or subjective craving between NAC and placebo during treatment or across sessions, or significant interaction. A significant treatment-by-time interaction, with reduced intrinsic connectivity was observed after treatment (T1) for NAC-treated compared to placebo-treated patients in the posterior cingulate node (9, left hemisphere) of the dorsal attentional network and connections to salience, ventral-attentional, somatosensory, and visual-peripheral networks implicated in AUD. NAC reduced intrinsic functional connectivity in patients with moderate-severe AUD after treatment compared to placebo, but did not attenuate alcohol cue-elicited activation. However, the absence of cue reactivity findings may result from low power, rather than the absence of cue reactivity findings associated with NAC. These results provide preliminary evidence that NAC treatment may modulate intrinsic functional connectivity brain activation in patients with alcohol use disorder, but replication in larger studies are required to determine the strength of this effect and any associations with clinical outcomes. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT03879759.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}