Clinical Neuropharmacology最新文献

Objectives: Traditional antidepressant therapy is associated with an inadequate response and a low remission rate. Our aim was to synthesize published randomized controlled trials on the potential effects of minocycline in patients with depression.

Methods: PubMed, Web of Science, Embase, and Cochrane Library databases were searched for studies published. Randomized controlled trials published in English that evaluated the efficacy of minocycline in patients with depression were selected for inclusion. Changes from baseline in the Hamilton Depression Rating Scale (HDRS) or Montgomery-Åsberg Depression Rating Scale (MADRS) were pooled to determine the antidepressant effect of minocycline compared with placebo. The quality of the included studies was assessed using the Cochrane risk-of-bias tool.

Results: Eight trials with 567 participants were eligible and included in the analysis. The meta-analysis did not reveal a statistically significant effect of minocycline on depression based on HDRS or MADRS scores.

Conclusions: According to the HDRS and MADRS scores, minocycline did not demonstrate effectiveness in reducing depressive symptoms.

Introduction: Adjunctive therapies to treat OFF episodes resulting from long-term levodopa treatment in Parkinson disease (PD) are hampered by safety and tolerability issues. Istradefylline offers an alternative mechanism (adenosine A2A receptor antagonist) and therefore potentially improved tolerability.

Methods: A systematic review of PD adjuncts published in 2011 was updated to include randomized controlled trials published from January 1, 2010-April 15, 2019. Pairwise meta-analyses were updated, and Bucher indirect comparisons were used to generate estimates of relative safety, presented as odds ratio (OR) and 95% confidence interval (CI) for comparators versus istradefylline.

Results: Fifty-seven randomized controlled trials involving 11,517 patients were included in the meta-analysis. Relative to istradefylline, dopamine agonists and catechol-O-methyl transferase (COMT) inhibitors had statistically significant higher odds of dyskinesia and somnolence. Monoamine oxidase-B inhibitors had significantly higher odds of hypotension. Amantadine extended-release (ER) had statistically significant higher odds of hallucination, orthostatic hypotension, insomnia, and withdrawals due to adverse events. All interventions combined had significantly higher odds of dyskinesia versus istradefylline 20 mg and somnolence versus istradefylline 40 mg. Considering overall incidence of adverse events, COMT inhibitors and amantadine ER had statistically significant higher odds versus both istradefylline doses (COMT versus istradefylline 40 mg, OR: 1.33; 95% CI: 1.03, 1.75; versus istradefylline 20 mg, OR: 1.32; 95% CI: 1.01, 1.72; amantadine ER versus istradefylline 40 mg, OR: 3.45; 95% CI: 1.85, 6.25; versus istradefylline 20 mg, OR: 3.33; 95% CI: 1.82, 6.25).

Conclusion: Istradefylline was associated with a generally favorable safety profile relative to other adjunct medications in this study.

Objectives: This scoping review aimed to synthesize the existing data about psilocybin pharmacokinetics to learn what has been described regarding body disposition and safety when psilocybin was used in controlled research settings.

Methods: We performed a scoping literature review following the framework proposed by the JBI manual for evidence synthesis. Controlled clinical trials reporting pharmacokinetic data of psilocybin were considered appropriate for inclusion. We extracted the data on psilocybin pharmacokinetics and summarized it from the available literature on this topic. We also performed an exploratory-descriptive analysis using study level data to examine the relationship between dose of psilocybin and maximum serum concentrations (Cmax).

Results: We initially identified 850 articles, of which 5 were included. These trials included 112 healthy volunteers who received psilocybin in a controlled clinical setting. The peak concentration of psilocin in plasma (Cmax) ranged from 8.2 ng/mL to 37.2 ng/mL (median = 17, IQR = 11.9 to 23.5). The maximal concentrations (Cmax) of psilocin were reached (Tmax) around 2 hours, ranging from 1.7 hours to 2.2 hours (median = 2, IQR = 1.9 to 2.1) after psilocybin oral administration. Elimination half-life was between 1.2 hours and 3.3 hours (median = 2.0, IQR = 1.6 to 2.8). A strong positive relationship between dose and Cmax ( R2 = 0.95) was found. No serious adverse events were observed. We did not find studies reporting pharmacokinetic data from patients with depression or cancer patients transitioning to palliative care.

Conclusions: In summary, this review unveils oral psilocybin pharmacokinetics in healthy adults, revealing gaps in its application to target populations like those with depression or in palliative care.

Objective: Gliomas are a general designation for neuroepithelial tumors derived from the glial cells of the central nervous system. According to the histopathological and immunohistochemical features, the World Health Organization classifies gliomas into four grades. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor that has been approved for the treatment of glioblastoma multiforme (GBM) as a second-line therapy. However, its efficacy remains limited. Rho/Rho-associated kinase (ROCK) is a downstream molecule of small guanosine triphosphatases (GTPases) that regulates multiple cellular processes, including motility, migration, and proliferation. Thus, ROCK has been regarded as a therapeutic target for cardiovascular diseases, neurological diseases, immune diseases, and cancer, and ROCK inhibitors have high potential clinical value.

Methods: Viability rate of cells was detected using MTT assay, and apoptosis of cells was detected using FACS. Expression of target genes and proteins was detected using qPCR and western blotting analysis. Concentration of cytokines was detected using ELISA methods.

Results: Viability and migration of GBM cells were reduced after bevacizumab treatment and that these effects were enhanced by ROCK2 inhibition. We further found that ROCK2 inhibition promoting the effect of bevacizumab was mainly mediated by the RhoA/ROCK2 pathway, further inducing apoptosis in GBM cells. In addition, we found that angiogenesis and degradation of cellular matrix-related cytokines were reduced by ROCK2 inhibition.

Conclusions: ROCK2 inhibition contributes to the therapeutic effects of bevacizumab.

Objective: Insomnia is a frequent and difficult disease to treat. The objective was to determine the pharmacological management of a group of patients diagnosed with acute and chronic insomnia.

Methods: This is a cross-sectional study that identified patterns of prescription of drugs for outpatient use in patients with insomnia from a population database of 8.5 million individuals in the Health System of Colombia. Sociodemographic and pharmacological variables were considered.

Results: A total of 5825 patients with insomnia were identified. Acute insomnia was the most frequent complaint (85.2%). A total of 76.9% received pharmacological treatment, mainly through off-label drugs (70.7%), such as trazodone (20.2%), quetiapine (12.3%), and clonazepam (11.1%). The approved drugs were used in 9.9% of the patients, especially eszopiclone (4.7%) and zopiclone (3.6%). Benzodiazepines and Z compounds predominated in the elderly and individuals with chronic insomnia.

Conclusions: The pharmacological treatment of insomnia in this group of patients is heterogeneous, and medications not approved for this indication are very frequently used.

Objectives: Multiple sclerosis (MS)-related tremor remains a disabling problem that often responds poorly to medical treatments. This study aims to evaluate the effect of botulinum toxin type A on MS-related upper limb tremor.

Methods: This retrospective observational cohort study included 8 patients who received intramuscular injections of onabotulinum toxin type A for medically refractory MS-related tremor. Hospital records before and 4-6 weeks after treatment, including the Fahn-Tolosa-Marin Tremor rating scale (FTM-TRS), electrophysiological tremor analysis, neurological examination findings, and videos, were reviewed retrospectively.

Results: There was significant improvement after botulinum toxin injection in the FTM TRS part A score for tremor ( P = 0.011), FTM TRS part B score for hand function ( P = 0.011), FTM Part score for activities of daily living ( P = 0.012), and FTM TRS total score for overall evaluation ( P = 0.012). Electrophysiological tremor analysis revealed maximal tremor amplitudes between 700-2000 μV (before treatment) and between 300-1000 μV (after treatment). The mean tremor amplitudes before and after treatment were 1350 μV and 725 μV, respectively. No adverse reactions were observed after botulinum toxin treatment.

Conclusions: BoNT may improve upper limb tremor and functionality in MS-related tremor. The treatment involved administering BoNT under EMG guidance, with careful muscle selection based on clinical assessment and EMG findings. This approach aimed to optimize treatment efficacy while minimizing potential adverse effects. Further studies are warranted to confirm these findings.

Objectives: Our aim was to evaluate the comparative effects of sertraline and vortioxetine against stress-induced brain injury in rats.

Methods: The rats were assigned to a nonstress group (NSG), stress-treated control (StC), sertraline + stress (SSt), and vortioxetine + stress (VSt) groups. Sertraline and vortioxetine (10 mg/kg) were given orally by gavage to the SSt and VSt groups. One hour later, all animals (except NSG) underwent forced immobilization to establish a stress model (2 hours). The drugs were given once a day for 30 days. The animals were killed with ketamine 150 mg/kg, and tissues were removed from the cerebral cortex. One-way analysis of variance and Fisher post hoc least significant difference were conducted for the analysis.

Results: The malondialdehyde (nmol/mL) level was 2.58 ± 0.48 in the NSG, 8.09 ± 0.57 in the StC, 3.84 ± 0.53 in the SSt, and 2.84 ± 0.20 in the VSt group (P < 0.0002). The total glutathione (mmol/g) was 7.15 ± 0.59 in the NSG, 2.41 ± 0.43 in the StC, 4.58 ± 0.26 in the SSt, and 5.98 ± 0.13 in the VSt (P < 0.0002). The total oxidant status (mmol H2O2Eq/L) level was 3.56 ± 0.20 in the NSG, 9.99 ± 0.74 in the StC, 4.97 ± 0.39 in the SSt, and 3.81 ± 0.31 in the VSt (P < 0.0002). The total antioxidant status (mmolTroloxEq/L) level was 8.65 ± 0.37 in the NSG, 3.04 ± 0.22 in the StC, 6.29 ± 0.34 in the SSt, and 7.61 ± 0.40 in the VSt (P < 0.0002). Sertraline reduced pericellular edema in astrocytes and oligodendrocytes and decreased perivascular edema, dilatation, and congestion of blood vessels, whereas these were not seen with vortioxetine.

Conclusions: Compared with sertraline, vortioxetine is a neuroprotective antidepressant with higher antioxidant activity and can more effectively prevent stress-induced brain tissue injury.

Abstract: Dostoyevsky's novels raise profound ethical, moral, philosophical and theological issues and, as a result, both he and his novels serve as fertile subjects of scholarly inquiry across a variety of academic disciplines. In particular, major characters in "The Brothers Karamazov" lend themselves to classical psychodynamic formulations, such as the influence of adverse childhood experiences on adult social and occupational outcomes, which in the case of Dmitry, the eldest son of Fyodor Pavlovich Karamazov, are considered in exquisitely fine detail. Prosecutor and defense attorney provide differing interpretations of how early traumas, largely due to paternal neglect and abuse, affected Dmitry's adult outcome in the climactic trial over his alleged patricide. The novel also captures an extreme, and perhaps fanciful, description of an Oedipal rivalry between Dmitry and his father for the affection of a love interest leading to tragic and unpredictable consequences for both. The novel has been dissected by scholars across a variety of diverse and seemingly unrelated disciplines and continues to serve as a springboard for collaborative discussion. Re-reading the novel led the authors to wonder if translational developments in clinical neuroscience could further understanding of poor developmental trajectories of the novel's characters, as well as offer therapeutic recommendations for promoting more favorable occupational and social outcomes. Advances in basic neuroscience have been translated into actionable individualized, interdisciplinary, multimodal treatment plans leading to improved functional outcomes for children like Dmitry, Ivan, and Smerdyakov. Translational neuroscience enriches understanding of neurodevelopmental outcomes of characters in Dostoyevsky's novel "The Brothers Karamazov," especially in the context of genetic risk and in utero environmental insults.

Objective: Gliomas are a general designation for neuroepithelial tumors derived from the glial cells of the central nervous system. According to the histopathological and immunohistochemical features, the World Health Organization classifies gliomas into four grades. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor that has been approved for the treatment of glioblastoma multiforme (GBM) as a second-line therapy. However, its efficacy remains limited. Rho/Rho-associated kinase (ROCK) is a downstream molecule of small guanosine triphosphatases (GTPases) that regulates multiple cellular processes, including motility, migration, and proliferation. Thus, ROCK has been regarded as a therapeutic target for cardiovascular diseases, neurological diseases, immune diseases, and cancer, and ROCK inhibitors have high potential clinical value.

Methods: Viability rate of cells was detected using MTT assay, and apoptosis of cells was detected using FACS. Expression of target genes and proteins was detected using qPCR and western blotting analysis. Concentration of cytokines was detected using ELISA methods.

Results: Viability and migration of GBM cells were reduced after bevacizumab treatment and that these effects were enhanced by ROCK2 inhibition. We further found that ROCK2 inhibition promoting the effect of bevacizumab was mainly mediated by the RhoA/ROCK2 pathway, further inducing apoptosis in GBM cells. In addition, we found that angiogenesis and degradation of cellular matrix-related cytokines were reduced by ROCK2 inhibition.

Conclusions: ROCK2 inhibition contributes to the therapeutic effects of bevacizumab.