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Medicina Sep 2023Autism is a neurodevelopmental disorder characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors. Frequently... (Review)
Review
Autism is a neurodevelopmental disorder characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors. Frequently associated with sensory dysfunction, other neurodevelopmental disorders, neuropsychiatric disorders, epilepsy and/or sleep disorders. This condition will accompany people throughout their lives, which will generate various support and treatment needs. Although there are no drugs that modify the core symptoms of autism, various drugs have shown their usefulness in associated conditions. Atypical antipsychotics for hyperactivity, impulsivity, agitation, auto or heteroaggression crises. Serotonin reuptake inhibitors, to decrease anxiety, obsessive-compulsive symptoms, and irritability/agitation. Stimulants and atomoxetine used for hyperactivity, inattention, and impulsivity. Clonidine and guanfacine show some efficacy on hyperactivity and stereotyped behaviors. Buspirone has been used for restrictive behaviors and anxiety. There are drugs in the research phase such as oxytocin, vasopressin and even some developed for specific entities related to autism such as arbaclofen in Fragile X and Trofinetide that has just been approved for use in Rett syndrome. As specific entities and their pathophysiology are identified, it is likely that tailored treatments will be developed for each entity associated with autism..
Topics: Humans; Autistic Disorder; Stereotyped Behavior; Anxiety; Anxiety Disorders; Autism Spectrum Disorder
PubMed: 37714122
DOI: No ID Found -
Neuropharmacology Oct 2023The inbred mouse strain, BTBR TItpr3/J (BTBR), possesses neuronal and circuit abnormalities that underlie atypical behavioral profiles resembling the major symptoms of...
The inbred mouse strain, BTBR TItpr3/J (BTBR), possesses neuronal and circuit abnormalities that underlie atypical behavioral profiles resembling the major symptoms of human autism spectrum disorder (ASD). Forebrain serotonin (5-HT) transmission has been implicated in ASD-related behavioral alterations. In this study, we assessed 5-HT signals and the functional responsiveness in BTBR mice compared to standard C57BL/6J (B6) control mice to elucidate how 5-HT alterations contribute to behavioral abnormalities in BTBR mice. A lower number of 5-HT neurons in the median raphe, but not in the dorsal raphe, was observed in male and female BTBR mice. Acute systemic injection of buspirone, a 5-HT1A receptor agonist, induced c-Fos in several brain regions in both B6 and BTBR mice; however, blunted c-Fos induction in BTBR mice was documented in the cingulate cortex, basolateral amygdala (BLA), and ventral hippocampus (Hipp). Decreased c-Fos responses in these regions are associated with a lack of buspirone effects on anxiety-like behavior in BTBR mice. Analysis of mRNA expression following acute buspirone injection indicated that 5HTR1a gene downregulation (or upregulation) occurred in the BLA and Hipp of B6 mice, respectively, but not BTBR mice. The mRNA expression of factors associated with neurogenesis or the pro-inflammatory state was not consistently altered by acute buspirone injection. Therefore, 5-HT responsivity via 5-HT1A receptors in the BLA and Hipp are linked to anxiety-like behavior, in which circuits are disrupted in BTBR mice. Other distinct 5-HT circuits from the BLA and Hipp that regulate social behavior are restricted but preserved in BTBR mice.
Topics: Humans; Mice; Male; Female; Animals; Autistic Disorder; Autism Spectrum Disorder; Buspirone; Serotonin; Mice, Inbred C57BL; Mice, Inbred Strains; Social Behavior; Disease Models, Animal; Phenotype; RNA, Messenger
PubMed: 37301467
DOI: 10.1016/j.neuropharm.2023.109634 -
Cureus Sep 2023Excessive, uncontrollable, and usually unjustified worry about certain things is a sign of the mental and behavioral disease known as generalized anxiety disorder (GAD).... (Review)
Review
Excessive, uncontrollable, and usually unjustified worry about certain things is a sign of the mental and behavioral disease known as generalized anxiety disorder (GAD). Genetic research suggests that numerous genes are likely implicated in the development of GAD, even if much is yet unclear about this. As a result, if someone in a family has GAD, there is a high likelihood that someone else will also suffer from the illness, as well as another anxiety disorder. Individuals with GAD are frequently overly bothered about workaday affairs like health, assets, demise, family, accord issues, or effort challenges. Worry frequently interferes with daily functioning. Excessive concern, restlessness, difficulty sleeping, tiredness, irritability, sweating, and trembling are a few symptoms that may be present. For a formal diagnosis of GAD, symptoms must be persistent for at least six months and consistent. Conversion in the amygdala's utilitarian congruence and how it processes fear and anxiety have been linked to generalized anxiety disorder. Neurotransmitters, and particularly the gamma-aminobutyric acid (GABA) variant, have long been known to cause GAD through dysregulating amygdala activity in the brain. Anxiety, concern, or physical symptoms must significantly hinder social, academic, or occupational functioning in order to qualify for a GAD diagnosis. The Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) provides explicit ethos to aid doctors in identifying this disorder. Psychological therapy based on cognitive behavioral therapy (CBT) principles is effective in reducing anxiety symptoms for short-term treatment of GAD. In this, the patient's thinking ability and methods are focused. The main principle behind CBT is that your thought patterns affect your feelings, which in turn can affect your behavior. Drugs like antidepressants, buspirone, benzodiazepines, and can all be worn to goody GAD. Outside of therapy, patients with anxiety can learn to manage it by practicing relaxation methods, reframing unfavorable ideas, and adopting stress-relieving adjustments. Being socially active and setting aside time for proper self-care are crucial components of managing generalized anxiety disorder.
PubMed: 37900518
DOI: 10.7759/cureus.46115 -
Cureus May 2023The aim of this systematic review is to appraise the current evidence on the efficacy and safety of buspirone in core symptoms of autism spectrum disorder (ASD),... (Review)
Review
The aim of this systematic review is to appraise the current evidence on the efficacy and safety of buspirone in core symptoms of autism spectrum disorder (ASD), co-occurring anxiety, and other associated symptoms. Major medical literature databases were searched for randomized controlled trials (RCTs), open-label trials, and any other relevant studies or clinical trials reporting on pediatric (age < 18 years) patients with ASD treated with buspirone for any reason. A total of 310 abstracts were screened, and six clinical trials were selected for inclusion. Out of these six clinical trials, two were RCTs ( =166 and 40), two open-label trials (n= 26 and 4), and one cross-over study ( = 1). We also included one retrospective chart review (n=31). Meta-analysis was not performed due to a lack of homogeneity in the two RCTs. Although most of the studies reported improved overall symptoms, they had different outcome measures. The quality of evidence available is low, and there is a need for higher-power studies in the future. Most studies suggested that buspirone was well tolerated and safe in pediatric patients with ASD. Based on the data, there is insufficient evidence to make conclusive recommendations on buspirone for improvement in core symptoms of ASD or cooccurring anxiety, irritability, or hyperactivity symptoms in the pediatric population. Given there are limited approved therapies for co-occurring anxiety, buspirone could be used as a safe off-label option due to the lack of behavioral activation and any serious adverse reactions.
PubMed: 37378184
DOI: 10.7759/cureus.39304 -
Antioxidants (Basel, Switzerland) Dec 2023Chronic oxidative stress impairs the normal functioning of the retinal pigment epithelium (RPE), leading to atrophy of this cell layer in cases of advance age-related...
Chronic oxidative stress impairs the normal functioning of the retinal pigment epithelium (RPE), leading to atrophy of this cell layer in cases of advance age-related macular degeneration (AMD). The purpose of our study was to determine if buspirone, a partial serotonin 1A (5-HT1A) receptor agonist, protected against oxidative stress-induced changes in the RPE. We exposed differentiated human ARPE-19 cells to paraquat to induce oxidative damage in culture, and utilized a mouse model with sodium iodate (NaIO)-induced oxidative injury to evaluate the effect of buspirone. To investigate buspirone's effect on protective gene expression, we performed RT-PCR. Cellular toxicities and junctional abnormalities due to paraquat induction in ARPE-19 cells and buspirone's impact were assessed via WST-1 assays and ZO-1 immunostaining. We used spectral-domain optical coherence tomography (SD-OCT) and ZO-1 immunostaining of RPE/choroid for structural analysis. WST-1 assays showed dose-dependent protection of viability in buspirone-treated ARPE-19 cells in culture and preservation of RPE junctional integrity under oxidative stress conditions. In the NaIO model, daily intraperitoneal injection (i.p.) of buspirone (30 mg/kg) for 12 days improved the survival of photoreceptors compared to those of vehicle-treated eyes. ZO-1-stained RPE flat-mounts revealed the structural preservation of RPE from oxidative damage in buspirone-treated mice, as well as in buspirone-induced , , , , and genes in the RPE/choroid compared to untreated eyes. Since oxidative stress is implicated in the pathogenesis AMD, repurposing buspirone, which is currently approved for the treatment of anxiety, might be useful in treating or preventing dry AMD.
PubMed: 38136248
DOI: 10.3390/antiox12122129 -
Substance Abuse and Rehabilitation 2024Illicitly manufactured fentanyl (IMF) is a significant contributor to the increasing rates of overdose-related deaths. Its high potency and lipophilicity can complicate... (Review)
Review
Illicitly manufactured fentanyl (IMF) is a significant contributor to the increasing rates of overdose-related deaths. Its high potency and lipophilicity can complicate opioid withdrawal syndromes (OWS) and the subsequent management of opioid use disorder (OUD). This scoping review aimed to collate the current OWS management of study populations seeking treatment for OWS and/or OUD directly from an unregulated opioid supply, such as IMF. Therefore, the focus was on therapeutic interventions published between January 2010 and November 2023, overlapping with the period of increasing IMF exposure. A health science librarian conducted a systematic search on November 13, 2023. A total of 426 studies were screened, and 173 studies were reviewed at the full-text level. Forty-nine studies met the inclusion criteria. Buprenorphine and naltrexone were included in most studies with the goal of transitioning to a long-acting injectable version. Various augmenting agents were tested (buspirone, memantine, suvorexant, gabapentin, and pregabalin); however, the liberal use of adjunctive medication and shortened timelines to initiation had the most consistently positive results. Outside of FDA-approved medications for OUD, lofexidine, gabapentin, and suvorexant have limited evidence for augmenting opioid agonist initiation. Trials often have low retention rates, particularly when opioid agonist washout is required. Neurostimulation strategies were promising; however, they were developed and studied early. Precipitated withdrawal is a concern; however, the rates were low and adequately mitigated or managed with low- or high-dose buprenorphine induction. Maintenance treatment continues to be superior to detoxification without continued management. Shorter induction protocols allow patients to initiate evidence-based treatment more quickly, reducing the use of illicit or non-prescribed substances.
PubMed: 38623317
DOI: 10.2147/SAR.S433358 -
Heliyon Apr 2024Buspirone, a 5-hydroxytryptamine 1A (5-HT1A) receptor agonist, has been investigated for its use in various diseases. However, knowledge about its side effects and...
Buspirone, a 5-hydroxytryptamine 1A (5-HT1A) receptor agonist, has been investigated for its use in various diseases. However, knowledge about its side effects and potential cognitive benefits in different conditions is limited. Cognitive impairment is also a prevalent symptom in many diseases, yet effective treatments are still lacking. Therefore, to explore the potential side effects of buspirone and the possible cognitive benefits of buspirone, we conducted a comprehensive search of several databases, including PubMed, Embase, Web of Science, Cochrane Review, Cochrane Trial, and ClinicalTrials.gov, to identify eligible randomized clinical trials. Our primary outcome measures included both side effects (adverse events) and cognitive benefits. For continuous variables, we utilized effect size with a 95% confidence interval (CI), whereas for dichotomous variables, we used odds ratios (OR) with a 95% CI. In total, 16 studies were included in this analysis, with 13 studies reporting on buspirone's side effects and 4 studies focusing on cognitive tasks. In terms of side effects, buspirone exhibited a higher rate of dizziness (OR = 4.66, 95% CI: 2.07-10.47), constipation (OR = 4.11, 95% CI: 1.34-12.55), and gastric distress (OR = 1.97, 95% CI: 1.03-3.78) than the placebo group. Regarding cognitive functions, buspirone showed significant benefits (g = 0.20, 95% CI: 0.06-0.34) while the placebo did not. Subgroup analysis indicated superior performance in visual learning and memory (g = 0.49, 95% CI: 0.21-0.78), logical reasoning (g = 0.42, 95% CI: 0.14-0.71), and attention (g = 0.37, 95% CI: 0.13-0.61) when compared to placebo. Our findings indicated that participants in the buspirone group experienced side effects of dizziness, constipation, and gastric distress in different diseases. Despite these adverse events, however, buspirone demonstrated significant cognitive benefits, particularly in the domains of visual learning and memory, logical reasoning, and attention.
PubMed: 38601569
DOI: 10.1016/j.heliyon.2024.e28918 -
Cureus Aug 2023A female in her early 40s taking buspirone, quetiapine, and daily kratom presented to the emergency department two days after starting a course of Paxlovid for a mild...
A female in her early 40s taking buspirone, quetiapine, and daily kratom presented to the emergency department two days after starting a course of Paxlovid for a mild COVID-19 infection with diffuse tremors, ocular clonus, diaphoresis, and confusion consistent with serotonin syndrome (SS). The patient was treated with oral lorazepam, and her symptoms significantly improved within one hour without the need for additional dosing. To our knowledge, this is the first reported case of SS in a COVID-19-positive patient who was prescribed Paxlovid. Clinicians should be mindful of the potential interactions of Paxlovid with serotonergic agents, and they should consider reducing the dose of these agents or selecting other therapeutics to treat COVID-19 infection in these patients.
PubMed: 37664331
DOI: 10.7759/cureus.42898