CNS Spectrums最新文献

Melatonin is an easily accessible, widely used drug for sleep issues, disrupted sleep-wake cycles, and jet lag, available in a variety of forms and dosages. Melatonin is also used in hospital settings to promote sleep onset, particularly in elderly patients, as a circadian rhythm regulator. Despite the popularity of melatonin, it is not approved by the US Food and Drug Administration (FDA). This creates ambiguity surrounding its proper usage for optimum results, including dosage and time of administration. The objective of this article is to shed light on the best timing to administer melatonin. Melatonin is a hormone that our body naturally produces to regulate our biological clock. Even though our body has a built-in "sleep system," many people still suffer from chronic sleep disorders such as insomnia. Melatonin has also proved to help prevent delirium in hospitalized patients due to its circadian rhythm regulatory effects. The elderly are at risk of developing insomnia because as one ages, melatonin production decreases. The most convenient solution for insomnia is to take melatonin supplements. To optimize the effects of melatonin supplements, proper dosage and timing must be considered. Additionally, patients who are oppositional to bedtime, which is known as bedtime resistance, are typically more willing to go to bed following melatonin administration. Melatonin administration at around 6 PM (1-2 hours before bedtime) is optimal to regulate sleep cycles of patients, and it can help with bedtime resistance. This should be the standard of care in all hospitals, nursing homes, and at home.

Two vesicular monoamine transporter 2 (VMAT2) inhibitors, valbenazine and deutetrabenazine, are approved for the treatment of tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Since their initial approval in 2017, new formulations and doses for both medications have become available, including a sprinkle capsule for valbenazine and a once-daily tablet for deutetrabenazine. In light of these new therapeutic options, a comprehensive scoping review was conducted to consolidate the current knowledge about these medications. Both valbenazine and deutetrabenazine are safe and effective in treating TD. However, as they are different drugs, one objective of this review is to describe their pharmacology and pharmacokinetics. Another objective is to summarize the similarities and differences as to how these medications are prescribed, specifically in terms of their warnings and precautions, their use in special populations, and recommendations for dosing when taken with concomitant medications. Results from double-blind, placebo-controlled clinical trials are presented, along with post hoc analyses that provide benchmarks for clinical relevance (eg, effect size, number needed to treat, minimal clinically important difference). As most patients with TD will require ongoing treatment, findings from long-term studies provide evidence for the safety and effectiveness of these medications.

Objectives: This proof-of-concept study aimed to assess the impact of intranasal esketamine (ESK-IN) in brain volume and neurofilament light chain (sNfL) over 6-months in patients with treatment resistant depression (TDR).

Methods: Seven TRD patients received ESK-IN while continuing oral antidepressants. Clinical evaluations were conducted at baseline, 1, 3, and 6 months, with MRI scans and blood samples taken at baseline and 6 months. Brain volume was assessed using VolBrain2 and DSI studio.

Results: Compared to controls, TRD patients initially showed lower volumes (mm³) in key cortical regions such as the insula (p = 0.0156), the frontal lobe (p = 0.0228) the superior parietal lobe (p = 0.0402), both superior (p = 0.0216) and inferior (p = 0.0437) temporal lobes and subcortical regions such as the nucleus accumbens (p = 0.0056), putamen (p = 0.0083), thalamus (p = 0.0102) and the hippocampus (p = 0.0001). Brain volume increased in the frontal cortex (p = 0.0295), the anterior cingulate (p = 0.0496), and hippocampus (p = 0.0015), as well as in the volume and fiber tracts associated with emotional regulation, such as the frontoparahippocampal (p = 0.0156 and p = 0.0313, respectively), the frontoparietal (p = 0.0496 and p = 0.0156, respectively) and the frontal aslant tract after 6 months on treatment with ESK-IN. In parallel, sNfL levels decreased post-treatment, indicating potential neuroprotective effects.

Conclusions: ESK-IN may promote structural changes in regions associated with mood regulation and neuroplasticity, while also reducing neuronal damage in TRD patients.

Objectives: Electroconvulsive therapy (ECT) is one of the most effective treatments for depression, but worries about cognitive side effects remain. This retrospective study evaluated cognitive outcomes and the antidepressant efficacy of ECT in a real-life sample of patients with treatment-resistant uni- or bipolar depression.

Methods: We included 90 depressed inpatients aged 49 ± 13.8 (SD) years who underwent 10 ± 2.1 (SD) unilateral or bitemporal ECT treatments and completed an extensive pre- and post-treatment psychological test battery. The Hamilton Depression Rating Scale (HAMD) and the Mini-Mental State Examination (MMSE) were evaluated as main outcomes pre-/post-ECT treatment.

Results: There was no significant change in MMSE scores between pre-/post-treatment assessments (β = 0.10, 95% confidence interval [CI] [-0.44, 0.25], p = 0.58), indicating no negative effect on global cognition. A minority of patients (N = 3) experienced a reduction of ≥5 points in the MMSE. Most cognitive tests showed no difference; however, some domains revealed statistically significant improvements (visual learning and motoric reaction time), whereas one domain showed a significant decline (verbal learning). Higher age and higher stimulus doses predicted worse outcomes in some cognitive domains. While ECT significantly reduced depressive symptoms measured by HAMD (β = -5.51, 95% CI [-7.08, -3.94], p < 0.001), depressive symptoms were not associated with cognitive outcomes.

Conclusions: No major cognitive changes were observed. While test results indicated deterioration in verbal learning and improvement in visual learning and motoric reaction time, effect sizes were small, and other cognitive tests showed no significant changes. The main limitation is the absence of retrograde memory assessment.

Parkinson's disease, the second most prevalent neurological disorder, is a multisystem neurodegenerative disease characterized by both motor and non-motor symptoms. Transcranial direct current stimulation (tDCS) is a non-invasive brain neuromodulation technique that has been shown to be effective in some neurological conditions and for some clinical outcomes. To evaluate the efficacy of tDCS combined with gait training in Parkinson's disease, compared to placebo, absence of treatment, conventional therapy, or other therapies. A systematic review and meta-analysis were performed in accordance with the PRISMA guidelines and registered in PROSPERO CRD42024542552. The literature search was conducted in PubMed, CINAHL, SPORT Discus, Web of Science, Scopus, MEDLINE, and Academic Search Ultimate (EBSCO) databases up to May 2024, limited to trials from the last 10 years. A total of 600 articles were identified; 9 were included in the systematic review and 8 in the meta-analysis. Significant intra-group changes were observed, but in the meta-analysis, no significant differences were seen between tDCS + gait training and tDCS placebo + gait training, although variables such as motor function slightly favored the combination (MD = -0.49; 95% CI [-1.55; 0.57], I² = 0%). The combination of tDCS and gait training could provide significant motor benefits in terms of gait speed, functional mobility, cadence, motor function, quality of life, 6MWT, coordination and dynamic balance, flexibility, and stretch resistance in patients with Parkinson's disease, but not in a more effective way than the same training without stimulation.

Objective: Treatment options are limited for depressive episodes in patients with bipolar II disorder. This post hoc analysis evaluated the efficacy of lumateperone in three pooled short-term, Phase 3 studies in patients with a major depressive episode (MDE) associated with bipolar II disorder.

Methods: This post hoc analysis pooled data from patients (18-75 years) with DSM-5 diagnosed bipolar II disorder experiencing an MDE in randomized, double-blind, placebo-controlled studies of lumateperone 42 mg monotherapy (Study 401, Study 404) and adjunctive therapy to lithium or valproate (Study 402). Primary and key secondary outcomes were change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total and Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) scores. Safety was also assessed.

Results: Lumateperone significantly improved MADRS Total score at Day 43 in the bipolar II population (placebo, n = 87; lumateperone, n = 87; least squares mean difference vs. placebo [LSMD], -4.0; P < .05). In the bipolar II population, lumateperone significantly improved CGI-BP-S Total (LSMD, -1.0; P < .05), Depression (LSMD, -0.5; P < .05), and Overall Bipolar Illness scores (LSMD, -0.5; P < .05) compared with placebo at Day 43. No new safety signals were identified, with minimal risk of extrapyramidal symptoms, cardiometabolic abnormalities, or prolactin elevation.

Conclusions: Lumateperone 42 mg monotherapy or adjunctive therapy significantly improved symptoms of depression and disease severity in patients with bipolar II disorder across Phase 3 studies. Lumateperone was generally well tolerated. These results support lumateperone 42 mg to treat MDEs associated with bipolar II disorder.

Clozapine is the gold standard for treatment-resistant schizophrenia. In the setting of malignancy with concurrent anti-cancer agent use, clozapine use may be of increased concern. Clozapine cessation holds its own risks. This study aims to systematically review all cases of concurrent pharmacotherapy with clozapine and anti-cancer agents and analyze the psychiatric and physical health outcomes. PubMed, EMBASE, CINAHL, and PsycINFO databases were searched from inception to February 2025. Descriptive statistics and narrative analysis of the included cases occurred. There were 53 cases of clozapine use with anti-cancer agents, with a male to female ratio of 1.7:1 and a mean age of 45.0 years. In 30 cases, clozapine was continued without interruption, and in additional 16 cases, clozapine was recommenced after a period of interruption. In cases with clozapine interruption or discontinuation, 90% noted significant deterioration in mental state despite alternative antipsychotic treatments. There were 34 cases of neutropenia, mostly (94%) in the setting of cytotoxic chemotherapy, with low rates of neutropenic complications. The successful continuation of clozapine with anti-cancer agents can occur, although risk-benefit analysis taking into account individual, clozapine, psychiatric, and physical health factors is required. Consideration of prophylactic neutropenia protective measures should form part of the discussion with the individual and their family.

This chapter discusses the Dutch Law on Compulsory Mental Healthcare (Wvggz), which aims to strengthen the autonomy of patients with severe mental disorders by recognizing that coercive measures can be used not only to prevent harm, but also to restore autonomy. This approach challenges the traditional notion that coercive measures inherently undermine autonomy. The chapter also explores the unintended consequences of the law, such as increased bureaucracy. We argue that while the Wvggz introduces valuable ideas, its practical implementation has highlighted the challenges of translating legislative goals into effective practices.

Objectives: Much work has been done on the role of trauma in obsessive-compulsive disorder (OCD), but the relationship between stressful life events (SLEs) and the onset of OCD remains poorly studied. This study aims to summarize the evidence about the association between SLEs and OCD development.

Methods: For this systematic review, we searched PubMed, Web of Science, Scopus, and PsycINFO databases for studies published from the database's inception to December 12, 2024. We included studies investigating the prevalence of SLEs among individuals diagnosed with OCD compared to other psychiatric disorders or healthy controls.

Results: Seven studies met the inclusion criteria and were incorporated. Two studies found that OCD patients suffered more SLEs than healthy controls in the year before the onset of OCD. Two of the included studies showed a higher occurrence of SLEs across the patients' lifetime before the onset of OCD. Three studies were comparable and, therefore, meta-analyzable. Together, they revealed that SLEs in the year before the onset of OCD were associated with a small yet positive pooled effect size.

Conclusions: Our review suggests that SLEs may be highly represented among people with OCD both in the year preceding the disorder's onset and throughout their lifetime.