Search Results (305)

Background: Medically unexplained oral symptoms/syndromes (MUOS), such as Burning Mouth Syndrome and Persistent Idiopathic Facial Pain, present significant management challenges due to the lack of standardized treatments and high-level evidence. While pharmacotherapy is often employed, real-world data on treatment adherence—a pragmatic proxy for effectiveness and tolerability—remain sparse, especially in Japan. This study aimed to describe the real-world prescribing patterns of antidepressants and dopamine receptor partial agonists (DPAs) for MUOS and retrospectively investigate their association with treatment continuation. Methods: This retrospective observational study analyzed data from patients initiating pharmacotherapy for MUOS at a specialized clinic in Japan (April 2021–March 2023). We used Cox proportional hazards models to evaluate treatment continuation for amitriptyline monotherapy and antidepressant–aripiprazole adjunctive therapy. The primary outcome was the time to discontinuation. Dosage effects were modeled using B-splines to capture nonlinearity. Results: Among 702 MUOS patients who started pharmacotherapy, 493 received amitriptyline as the first prescription, and 108 received aripiprazole as an adjunctive therapy. For amitriptyline monotherapy, a nonlinear relationship was observed between dosage and discontinuation risk, with a relatively lower hazard around 25 mg/day across age groups. In the antidepressant–aripiprazole adjunctive group, the overall hazard ratio for discontinuation was higher (HR = 4.75, p < 0.0005) compared to non-adjunctive therapy, likely due to indication bias reflecting more treatment-resistant cases. However, within the aripiprazole adjunctive group, a U-shaped relationship was identified between maximum aripiprazole dosage and discontinuation risk, with the lowest hazard (HR ≈ 0.30) observed at approximately 1.7–1.8 mg/day. Mild side effects such as drowsiness, dry mouth, constipation, tremor, insomnia, and weight gain were noted, but no severe adverse events occurred. Conclusions: This real-world data analysis suggests specific dosage ranges (amitriptyline ≈ 25 mg/day; aripiprazole augmentation ≈ 1.7–1.8 mg/day) are associated with longer treatment continuation in MUOS patients. Treatment continuation reflects a crucial balance between symptom relief and tolerability, essential for managing these chronic conditions. It is critical to emphasize that these findings are descriptive and observational, derived from a specialized setting, and do not constitute prescriptive recommendations. They highlight the importance of individualized dosing. Definitive evidence-based strategies require validation through prospective randomized controlled trials. Full article

Pituitary pars intermedia dysfunction (PPID) is a common, slowly progressive, neurodegenerative disorder of the older horse. Oxidative damage to the hypothalamic periventricular neurons results in loss of dopaminergic inhibition of the pars intermedia region of the pituitary gland. Consequently, there is increased production of the pro-opiomelanocortin (POMC)-derived hormones normally produced by this region, as well as initial melanocyte hypertrophy and hyperplasia, followed by adenomatous change. Clinical signs that are highly suggestive of the disease are generalised and regional hypertrichosis and delayed/abnormal coat shedding. Numerous clinical signs provide a moderate clinical suspicion, including hyperhidrosis, abnormal fat distribution/regional adiposity, epaxial muscle atrophy/loss of topline, laminitis, weight loss, recurrent infections, behavioural changes/lethargy, polyuria and polydipsia, a pot-bellied appearance, bulging supraorbital fat pads, reduced wound healing, lordosis and infertility. In all animals, a diagnosis of PPID is made based on the signalment, clinical signs and results of further diagnostic tests, with age being a crucial factor to consider. Currently recommended further diagnostic tests are measurement of basal adrenocorticotrophic hormone (ACTH) concentrations (all year) and evaluation of the ACTH response to thyrotrophin-releasing hormone (TRH) using seasonally adjusted references intervals (non-autumn). Animals should also be tested for insulin dysregulation, as laminitis risk in PPID is associated with hyperinsulinaemia. PPID can be managed but not cured; it is a lifelong condition. The individual clinical signs can be managed, e.g., clipping the excessive haircoat and providing unrestricted access to water for individuals with polydipsia. Alternatively, pharmacological management can be employed, and the dopamine-2 receptor agonist pergolide is licensed/approved for the treatment of equine PPID. This should be prescribed in combination with dietary recommendations based on the body condition score and insulin sensitivity status of the individual animal. Full article

This study presents the proof-of-concept design and preliminary implementation of a bioelectric biosensor based on an Arduino platform for real-time monitoring of gel-immobilized N2a neuroblastoma cells using dopamine as a model neurotransmitter. The sensor operates on the principle of bioelectric recognition assay (BERA), and uses a two-electrode set-up as a simple, cost-efficient way to capture electrophysiological responses following dopamine exposure, while at the same time mimicking the in vivo cellular environment. Cellular ohmic resistance was assessed under increasing dopamine concentrations and temperatures (24 °C and 37 °C). The results showed that temperature significantly affected cell responses to increasing dopamine concentrations, possibly because of differences in dopamine diffusion in gel, which may in turn have affected membrane polarization and overall cell electric resistance. Pending further testing against a wider range of dopamine concentrations along with various dopamine agonists/antagonists, as well as optimization in terms of specificity, selectivity, and sensitivity, the biosensor could be applied in bioscreening and neuropharmacological studies in a user-friendly, scalable way. Full article

Substance use disorders (SUDs) remain a major public health challenge, with existing pharmacotherapies offering limited long-term efficacy. Traditional treatments focus on dopaminergic systems but often overlook the complex interplay between metabolic signals, neuroplasticity, and conditioned behaviors that perpetuate addiction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes and obesity, have recently emerged as promising modulators of reward-related brain circuits. This review synthesizes current evidence on the role of glucagon-like peptide-1 (GLP-1) and its receptor in modulating craving and substance-seeking behaviors. We highlight how GLP-1 receptors are expressed in addiction-relevant brain regions, including the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC), where their activation influences dopaminergic, glutamatergic, and GABAergic neurotransmission. In addition, we explore how GLP-1 signaling affects reward processing through gut–brain vagal pathways, hormonal crosstalk, and neuroinflammatory mechanisms. Preclinical studies demonstrate that GLP-1RAs attenuate intake and relapse-like behavior across a range of substances, including alcohol, nicotine, and cocaine. Early-phase clinical trials support their safety and suggest potential efficacy in reducing craving. By integrating findings from molecular signaling, neurocircuitry, and behavioral models, this review provides a translational perspective on GLP-1RAs as an emerging treatment strategy in addiction medicine. We propose that targeting gut–brain metabolic signaling could provide a novel framework for understanding and treating SUDs. Full article

Background and aim of this review: The ongoing opioid epidemic underscores the urgent need for innovative pharmacological and behavioral interventions to mitigate the impact of opioid use disorder (OUD). This review aims to explore theoretical overlaps between the neurobiological mechanisms underlying OUD development and the pharmacodynamic profile of methylphenidate (MPH). Particular attention is given to the potential shared molecular targets, safety considerations, and therapeutic implications of MPH use in this clinical context. Main finding: In the development of opioid dependence, the negative reinforcement of the dopaminergic transmission of the mesocorticolimbic pathway induced by the supraspinal action of opioid receptor agonists plays a major role. The induced state of hypodopaminergic and hyperadrenergic modulates the underlying disease process by affecting cognitive control, affective regulation, and motivational drive. MPH, acting as a dopamine reuptake inhibitor and modulator of vesicular monoamine transporter 2 (VMAT-2), increases extracellular dopamine availability and enhances dopaminergic signaling, suggesting potential utility in restoring dopaminergic tone in OUD. Additionally, MPH has shown efficacy in hypoactive delirium in patients with terminal cancer, improving both cognitive function and psychomotor drive. Conclusions and future perspectives: There appear to be converging neurobiological mechanisms between the action of MPH and the pathophysiology of OUD, particularly within the dopaminergic system. However, well-designed clinical trials are essential to identify the patient subgroups that may benefit from adjunctive MPH treatment, to evaluate its efficacy in this setting, and to assess the long-term safety and risk profile of stimulant use in individuals with OUD. Full article

Background: Despite growing interest in the literature on Parkinson’s disease (PD) on cognitive functioning, financial incompetence—a crucial aspect of daily living—and its modulation susceptibility by PD treatment regimens remains relatively understudied. Objective: This systematic review and meta-analysis aimed to synthesize existing evidence on how PD treatments affect financial capacity, assessing both direct financial competence and cognitive or behavioral proxies of financial decision-making. Methods: A comprehensive literature search according to PRISMA protocol was conducted across major biomedical databases, supplemented by gray literature and manual reference list checks. Eligible studies assessed financial capacity directly or indirectly through cognitive proxies (e.g., executive function, decision-making) or financial risk behaviors (e.g., impulse control disorders). Two separate meta-analyses were performed. Heterogeneity (I²), publication bias (Egger’s test), and sensitivity analyses were conducted to assess robustness. Results: Twenty-three studies met inclusion criteria. One study directly measured financial capacity and was analyzed narratively, reporting diminished competence in patients on levodopa therapy. A meta-analysis of cognitive proxies (10 studies) showed a moderate effect size (Hedges’ g = 0.70, 95% CI [0.45, 0.92], p < 0.001), indicating that PD treatments negatively affect executive function and financial decision-making. A second meta-analysis of impulse control and financial risk behaviors (12 studies) revealed a larger effect size (Hedges’ g = 0.98, 95% CI [0.75, 1.22], p < 0.001), strongly linking dopamine agonists to increased financial risk-taking. Moderate heterogeneity (I² = 45.8–60.5%) and potential publication bias (Egger’s test p = 0.027) were noted. Conclusions: These findings suggest that PD treatments negatively impact financial decision-making both directly and indirectly through cognitive and behavioral pathways. Integrating financial decision-making assessments into PD care, particularly for patients on dopamine agonists, is recommended. Future research should prioritize longitudinal studies and standardized neuropsychological measures to guide clinical practice and optimize patient outcomes. Full article

When non-functioning pituitary adenomas (NFPAs) behave aggressively or recur after first-line surgical treatment, it can be challenging to decide whether and how to escalate therapy. Up to 47% of patients with residual tumor after transsphenoidal surgery will show disease recurrence or progression and may require an intervention. Repeat surgical resection can be attempted in select cases if the tumor is accessible; for the remainder of patients, non-surgical treatment options may need to be considered. Radiotherapy can control tumor growth in 75% of NFPAs, but confers increased risk of hypopituitarism and other disorders. Currently, there are no medical therapies approved for patients with recurrent or aggressive NFPA. However, several have been investigated, including temozolomide, somatostatin receptor ligands, dopamine agonists, immune checkpoint inhibitors, vascular endothelial growth factor inhibitors, and peptide receptor radionuclide therapy. We present a review of the available evidence to provide guidance for pituitary endocrinologists and neuro-oncologists when treating patients with recurrent or aggressive NFPA. Full article

Background/Objectives: Pituitary apoplexy (PA) is a rare medical emergency characterized by the sudden onset of symptoms resulting from hemorrhage and/or infarction within the pituitary gland. Precipitating factors include the use of dopamine agonists (DAs), whose main indication is the treatment of prolactin (PRL)-secreting pituitary neuroendocrine tumors (PitNETs), but which can also be considered in non-functioning PitNETs. Here we report a case of PA in a patient taking cabergoline for a non-functioning PitNET, followed by a review of the literature focusing on the cases of PA associated with the use of DAs. Methods: A review of the literature was performed, searching Pubmed for other clinical cases of PA associated with the use of DAs, from inception to March 2025. Results: We found 43 cases of PA associated with the use of DAs. All the patients had secreting tumors: 86% were classified as PRL-secreting PitNETs, 7% were classified as GH-secreting PitNETs, and 4.6% included a mixed PRL/GH-secreting PitNET and a TSH-secreting PitNET. By contrast, here we present a case of PA in a non-functioning PitNET during cabergoline therapy. Our patient was managed conservatively and endocrine function recovered spontaneously. In our case, cabergoline might have promoted PA, which is consistent with the reported efficacy of cabergoline in inducing tumor shrinkage of non-functioning PitNETs that express dopamine 2 receptors, including silent PIT1 and SF1 or NULL tumors. Conclusions: Our case confirms cabergoline efficacy in non-functioning PitNETs and sheds light on a possible complication of its use. Patients, particularly those with large tumors, should be closely monitored for this occurrence. Full article

The MAM domain-containing glycosylphosphatidylinositol anchor 1 (MDGA1) gene, which encodes a protein involved in synaptic inhibition, has been identified as a potential risk gene for restless legs syndrome. A recent study in the Chinese population described increased MDGA1 methylation levels in patients with idiopathic RLS (iRLS) compared to healthy controls. In this study, we investigated the possible association between the most common variants in the MDGA1 gene and the risk for iRLS in a Caucasian Spanish population. We assessed the frequencies of MDGA1 rs10947690, MDGA1 rs61151079, and MDGA1 rs79792089 genotypes and allelic variants in 263 patients with idiopathic RLS and 280 healthy controls using a specific TaqMan-based qPCR assay. We also analyzed the possible influence of the genotype frequencies on several variables, including age at the onset of RLS, gender, a family history of RLS, and response to drugs commonly used in the treatment of RLS. The frequencies of the genotypes and allelic variants of the three common missense SNVs studied did not differ significantly between RLS patients and controls, neither in the whole series nor when analyzing each gender separately; were not correlated with age at onset and the severity of RLS assessed by the International Restless Legs Syndrome Study Group Rating Scale (IRLSSGRS); and were not related to a family history of RLS or the pharmacological response to dopamine agonists, clonazepam, or gabaergic drugs. Our findings suggest that common missense SNVs in the MDGA1 gene are not associated with the risk of developing idiopathic RLS in Caucasian Spanish people. Full article

Background/Objectives: Dopamine partial agonists are drugs initially developed to treat schizophrenia, seeking a double effect of increased dopaminergic transmission in the prefrontal cortex and decrease in the accumbens/striatum. Of these drugs, aripiprazole, brexpiprazole, and cariprazine are currently marketed and used in schizophrenia spectrum and mood disorders. It is debated whether patients with psychiatric disorders becoming pregnant should discontinue or continue their antipsychotic treatment despite some risks for the fetus, i.e., whether it is worse to have an untreated disorder or treating it with drugs. The safety of drugs for mother and baby extend from pregnancy to the postpartum, when breastfeeding assumes great importance. We set to investigate the use of dopamine partial agonists in pregnancy and lactation. Methods: On 23 June 2025, we used suitable strategies for identifying cases and studies of cariprazine, aripiprazole, brexpiprazole, dopamine partial agonists in pregnancy, perinatal period, and/or lactation on PubMed, CINAHL, PsycInfo/PsycArticles, Scopus, and ClinicalTrials.gov. We used the PRISMA Statement in developing our review. We included case reports and clinical studies. We excluded reports without pregnancy or focused on other drugs than the above. We reached consensus on eligibility with Delphi rounds among all authors. Results: Our searches produced 386 results on the above databases. We included 24 case reports/series and 15 studies. Most studies showed no negative pregnancy outcomes. There were serious concerns about the use of dopamine D₂/D₃ partial agonists during lactation. Conclusions: The use of dopamine partial agonists during pregnancy appears to be safe, but during breastfeeding they should be better avoided. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are long-acting drugs that have gathered a lot of attention worldwide for their utility in the treatment landscape of type 2 diabetes mellitus and obesity. Their widespread global use has been accompanied by an additional observation related to a potential reduction in alcohol consumption. Preclinical studies in animal models, along with preliminary clinical findings, suggest that GLP-1 RAs may exert beneficial effects on alcohol use disorder (AUD). The latter represents a significant public health challenge, contributing to a broad spectrum of health, social, and economic burdens. Concurrently, the use of GLP-1 RAs in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) has been associated with a clinically meaningful reduction in all-cause mortality, major cardiovascular events, and progression to metabolic dysfunction-associated steatohepatitis (MASH). In this current opinion article, we firstly summarize the current literature dealing with the effect of GLP-1 RAs on AUD based on findings from experimental and human clinical studies. Additionally, beyond their role in MASLD, we explore in detail the potential impact of GLP-1 RAs on patients with alcoholic liver disease (ALD) and metabolic and alcohol-related/associated liver disease (MetALD). Finally, we highlight current challenges and unresolved issues, including concerns related to safety, accessibility, cost, and limitations in the clinical application of GLP-1 RAs. Full article

Clinically nonfunctioning pituitary tumors (CNFPTs) typically do not cause hormonal excess, progress insidiously, and are often large and invasive at presentation. Complete resection is frequently not attainable; radiotherapy (RT) may effectively limit growth but carries a significant risk of hypopituitarism. Medical therapy with dopamine D2 receptor agonists and/or somatostatin analogs has been explored in CNFPTs but have yielded inconsistent results, and there is an unmet need for novel efficacious and safe medical therapies. The authors used the PubMed database to identify and review articles published from January 1982 to July 2024, that discussed the medical treatment of CNFPTs. The most commonly studied medical therapies were somatostatin receptor ligands (SRLs) and dopamine D2 receptor agonists. Of 111 patients with CNFPTs treated with SRLs, 31 (28%) exhibited tumor shrinkage. Following dopamine agonist treatment in 355 patients, tumor shrinkage occurred in 113 (32%), tumor stabilization in 182 (51%), and tumor growth in 60 (17%). The efficacy of other less commonly employed therapies such as GnRH analogs, PRRT, and temozolomide was also reviewed. Efficacious and safe medical therapies evaluated in robust randomized placebo-controlled clinical trials are needed to improve the management of CNFPTs. Full article

Background/Objectives: Creativity is a complex cognitive process influenced by multiple factors, including neurobiological mechanisms and neurotransmitter regulation. In Parkinson’s disease (PD), dopaminergic therapy has been associated with both increases and decreases in creative output, raising questions about its underlying mechanisms and clinical relevance. Methods: A scoping review was conducted following the PRISMA guidelines to evaluate studies assessing the effects of dopaminergic therapy on creativity in PD patients. The search was performed in January 2025 across PubMed, Scopus, Web of Science, and Embase databases using predefined search terms. Results: Seven studies met the inclusion criteria, reporting mixed outcomes. Some found enhanced artistic expression and divergent thinking in patients treated with dopamine agonists, while others observed no significant change. Increased creativity appeared more common in individuals with pre-existing artistic tendencies rather than as a new emergence due to medication. Conclusions: Dopaminergic therapy may amplify pre-existing creative inclinations in PD patients but does not consistently induce creativity across individuals. Full article

Background/Objectives: G protein-coupled trace amine-associated receptors (TAARs) belong to a family of biogenic amine-sensing receptors. TAAR1 is the best-investigated receptor of this family, and TAAR1 agonists are already being tested in clinical studies for the treatment of schizophrenia, anxiety, and depression. Meanwhile, other TAARs (TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9 in humans) are mostly known for their olfactory function, sensing innate odors. At the same time, there is growing evidence that these receptors may also be involved in brain function. TAAR8 is the least studied TAAR family member, and currently, there is no data on its function in the mammalian central nervous system. Methods: We generated triple knockout (tTAAR8-KO) mice lacking all murine Taar8 isoforms (Taar8a, Taar8b, and Taar8c) using CRISPR-Cas9 technology. In this study, we performed the first phenotyping of tTAAR8-KO mice for behavioral, electrophysiological, and neurochemical characteristics. Results: During the study, we found a number of alterations specific to tTAAR8-KO mice compared to controls. tTAAR8-KO mice demonstrated better short-term memory, more depressive-like behavior, and higher body temperature. Also, we observed changes in the dopaminergic system, brain electrophysiological activity, and adult neurogenic functions in mice lacking Taar8 isoforms. Conclusions: Based on the data obtained, it can be assumed that the physiological TAAR8 role is not limited only to the innate olfactory function, as previously proposed. TAAR8 could be involved in brain function, in particular in dopamine function regulation. Full article

Glucagon-like peptide-1 receptor agonists, originally developed for the treatment of metabolic disorders, have recently emerged as promising candidates for the management of substance use disorders. This review synthesizes preclinical, clinical, and translational evidence on the effects of glucagon-like peptide-1 receptor agonists across addiction models involving alcohol, nicotine, psychostimulants, and opioids. In animal studies, glucagon-like peptide-1 receptor agonists consistently reduce drug intake, attenuate dopamine release in reward circuits, and decrease relapse-like behavior. Clinical and observational studies provide preliminary support for these findings, particularly among individuals with comorbid obesity or insulin resistance. However, several translational barriers remain, including limited blood–brain barrier penetration, species differences in pharmacokinetics, and variability in treatment response due to genetic and metabolic factors. Ethical considerations and methodological heterogeneity further complicate clinical translation. Future directions include the development of central nervous system penetrant analogues, personalized medicine approaches incorporating pharmacogenomics, and rigorously designed trials in diverse populations. Glucagon-like peptide-1 receptor agonists may offer a novel therapeutic strategy that addresses both metabolic and neuropsychiatric dimensions of addiction, warranting further investigation to define their role in the evolving landscape of substance use disorder treatment. Full article