-
American Family Physician Oct 2000Patients with generalized anxiety disorder experience worry or anxiety and a number of physical and psychologic symptoms. The disorder is frequently difficult to... (Review)
Review
Patients with generalized anxiety disorder experience worry or anxiety and a number of physical and psychologic symptoms. The disorder is frequently difficult to diagnose because of the variety of presentations and the common occurrence of comorbid medical or psychiatric conditions. The lifetime prevalence is approximately 4 to 6 percent in the general population and is more common in women than in men. It is often chronic, and patients with this disorder are more likely to be seen by family physicians than by psychiatrists. Treatment consists of pharmacotherapy and various forms of psychotherapy. The benzodiazepines are used for short-term treatment, but because of the frequently chronic nature of generalized anxiety disorder, they may need to be continued for months to years. Buspirone and antidepressants are also used for the pharmacologic management of patients with generalized anxiety disorder. Patients must receive an appropriate pharmacologic trial with dosage titrated to optimal levels as judged by the control of symptoms and the tolerance of side effects. Psychiatric consultation should be considered for patients who do not respond to an appropriate trial of pharmacotherapy.
Topics: Anti-Anxiety Agents; Anxiety Disorders; Benzodiazepines; Depressive Disorder, Major; Diagnosis, Differential; Humans; Panic Disorder; Patient Education as Topic; Teaching Materials
PubMed: 11037076
DOI: No ID Found -
Journal of Child and Adolescent... Feb 2018An increasing number of abandoned clinical trials have forestalled efforts to advance the evidence base for the treatment of mood and anxiety disorders in children and... (Review)
Review
OBJECTIVES
An increasing number of abandoned clinical trials have forestalled efforts to advance the evidence base for the treatment of mood and anxiety disorders in children and adolescents. With this in mind, we sought to present and validate a Bayesian approach for the reanalysis of summary data in abandoned clinical trials and to review and re-evaluate available pharmacokinetic, tolerability, and efficacy data from two large, randomized controlled trials of buspirone in pediatric patients with generalized anxiety disorder (GAD).
METHODS
Prospective, randomized, parallel-group controlled trials of buspirone in pediatric patients with GAD as well as associated pharmacokinetic studies were identified and data were extracted. In addition to descriptive statistics, marginal posterior densities for each variable of interest were determined and a Monte Carlo pseudosample was generated with random draws obtained from the Student's t-distribution to assess, with inferential statistics, differences in variables of interest.
RESULTS
Buspirone was evaluated in one flexibly dosed (N = 227) and one fixed-dose (N = 341) trial in children and adolescents aged 6-17 years with a primary diagnosis of GAD. With regard to improvement in the sum of the Columbia Schedule for Affective Disorders and Schizophrenia GAD items, buspirone did not separate from placebo in the fixed-dose trial at low (95% CI: -0.78 to 2.39, p = 0.32) or high dose (95% CI: -0.87 to 1.87, p = 0.47) nor did it separate from placebo in the flexibly dosed study (95% CI: -0.3 to 1.9, p = 0.15). Drop out as a result of a treatment-emergent adverse event was significantly greater in buspirone-treated patients compared to placebo (p = 0.011). Side effects were consistent with the known profile of buspirone with lightheadedness occurring more frequently in buspirone-treated patients (p < 0.001).
CONCLUSIONS
Buspirone is well tolerated in pediatric patients with GAD, although two randomized controlled trials were underpowered to detect small effect sizes (Cohen's d < 0.15). Finally, Bayesian approaches may facilitate re-examination of data from abandoned clinical trials.
Topics: Adolescent; Anti-Anxiety Agents; Anxiety Disorders; Bayes Theorem; Buspirone; Child; Humans; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 28846022
DOI: 10.1089/cap.2017.0060 -
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 -
Substance Abuse and Rehabilitation 2017The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders (CUDs) () and cannabis dependence (International Classification of Diseases [ICD]-10).... (Review)
Review
The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders (CUDs) () and cannabis dependence (International Classification of Diseases [ICD]-10). Several lines of evidence from animal and human studies indicate that cessation from long-term and regular cannabis use precipitates a specific withdrawal syndrome with mainly mood and behavioral symptoms of light to moderate intensity, which can usually be treated in an outpatient setting. Regular cannabis intake is related to a desensitization and downregulation of human brain cannabinoid 1 (CB1) receptors. This starts to reverse within the first 2 days of abstinence and the receptors return to normal functioning within 4 weeks of abstinence, which could constitute a neurobiological time frame for the duration of CWS, not taking into account cellular and synaptic long-term neuroplasticity elicited by long-term cannabis use before cessation, for example, being possibly responsible for cannabis craving. The CWS severity is dependent on the amount of cannabis used pre-cessation, gender, and heritable and several environmental factors. Therefore, naturalistic severity of CWS highly varies. Women reported a stronger CWS than men including physical symptoms, such as nausea and stomach pain. Comorbidity with mental or somatic disorders, severe CUD, and low social functioning may require an inpatient treatment (preferably qualified detox) and post-acute rehabilitation. There are promising results with gabapentin and delta-9-tetrahydrocannabinol analogs in the treatment of CWS. Mirtazapine can be beneficial to treat CWS insomnia. According to small studies, venlafaxine can worsen the CWS, whereas other antidepressants, atomoxetine, lithium, buspirone, and divalproex had no relevant effect. Certainly, further research is required with respect to the impact of the CWS treatment setting on long-term CUD prognosis and with respect to psychopharmacological or behavioral approaches, such as aerobic exercise therapy or psychoeducation, in the treatment of CWS. The up-to-date ICD-11 Beta Draft is recommended to be expanded by physical CWS symptoms, the specification of CWS intensity and duration as well as gender effects.
PubMed: 28490916
DOI: 10.2147/SAR.S109576 -
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 -
Prague Medical Report 2020Buspirone (BUS) belongs to the azapirone chemical class. The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms,... (Review)
Review
Buspirone (BUS) belongs to the azapirone chemical class. The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of BUS-associated movement disorders (MD). Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 25 reports containing 65 cases were assessed. The MD associated with BUS were: dyskinesia in 14 cases, 10 of akathisia, 8 of myoclonus, 6 of Parkinsonism, and 6 of dystonia. The cases not clearly defined were 7 tension, 14 incoordination, and the undefined number of dyskinesia, tics, and Parkinsonism. The mean age was 45.23 years (range: 15-74). The male was the predominant sex in 60.86% and the most common BUS-indication was anxiety disorder. The mean BUS-dose was 42.16 mg (range: 5-100). The time from the beginning of BUS administration to the MD onset was one month or less in 76%. The time from BUS withdrawal to complete recovery was within one month in 87.5%. The most common management was BUS withdrawal. In 16 patients the follow-up was reported: 14 had a full recovery, but in two (1 dyskinesia + 1 dystonia) the symptoms continued after the BUS withdrawal. MD associated with BUS were scarcely reported in the literature. Moreover, in the majority of cases, no clear description of the clinical profile, neurological examination, or the time data of the movement disorder onset and recovery were given.
Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Buspirone; Humans; Male; Middle Aged; Movement Disorders; Young Adult
PubMed: 32191616
DOI: 10.14712/23362936.2020.1 -
BMJ Clinical Evidence Oct 2011Up to one in five people may have generalised anxiety disorder (GAD) at some point, and most have other health problems. Less than half of people have full remission... (Review)
Review
INTRODUCTION
Up to one in five people may have generalised anxiety disorder (GAD) at some point, and most have other health problems. Less than half of people have full remission after 5 years. GAD may have a genetic component, and has also been linked to previous psychological or other trauma.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for GAD? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 74 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: abecarnil, antidepressants (duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, opipramol, paroxetine, sertraline, and venlafaxine), antipsychotic drugs (trifluoperazine), applied relaxation, benzodiazepines, buspirone, cognitive behavioural therapy, hydroxyzine, and pregabalin.
Topics: Anxiety Disorders; Benzodiazepines; Buspirone; Humans; Hydroxyzine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 22030083
DOI: No ID Found -
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 -
The Cochrane Database of Systematic... Jan 2019Globally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.This is an update of a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Globally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.This is an update of a Cochrane Review first published in the Cochrane Library in Issue 12, 2014.
OBJECTIVES
To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use.
SEARCH METHODS
We updated our searches of the following databases to March 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and Web of Science.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs involving the use of medications to treat cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in people diagnosed as cannabis dependent or who were likely to be dependent.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 21 RCTs involving 1755 participants: 18 studies recruited adults (mean age 22 to 41 years); three studies targeted young people (mean age 20 years). Most (75%) participants were male. The studies were at low risk of performance, detection and selective outcome reporting bias. One study was at risk of selection bias, and three studies were at risk of attrition bias.All studies involved comparison of active medication and placebo. The medications were diverse, as were the outcomes reported, which limited the extent of analysis.Abstinence at end of treatment was no more likely with Δ-tetrahydrocannabinol (THC) preparations than with placebo (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.64 to 1.52; 305 participants; 3 studies; moderate-quality evidence). For selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine, there was no difference in the likelihood of abstinence at end of treatment compared to placebo (low- to very low-quality evidence).There was qualitative evidence of reduced intensity of withdrawal symptoms with THC preparations compared to placebo. For other pharmacotherapies, this outcome was either not examined, or no significant differences was reported.Adverse effects were no more likely with THC preparations (RR 1.02, 95% CI 0.89 to 1.17; 318 participants; 3 studies) or N-acetylcysteine (RR 0.94, 95% CI 0.71 to 1.23; 418 participants; 2 studies) compared to placebo (moderate-quality evidence). For SSRI antidepressants, mixed action antidepressants, buspirone and N-acetylcysteine, there was no difference in adverse effects compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of withdrawal from treatment due to adverse effects with THC preparations, SSRIs antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of treatment completion with THC preparations, SSRI antidepressants, mixed action antidepressants and buspirone compared to placebo (low- to very low-quality evidence) or with N-acetylcysteine compared to placebo (RR 1.06, 95% CI 0.93 to 1.21; 418 participants; 2 studies; moderate-quality evidence). Anticonvulsants and mood stabilisers appeared to reduce the likelihood of treatment completion (RR 0.66, 95% CI 0.47 to 0.92; 141 participants; 3 studies; low-quality evidence).Available evidence on gabapentin (anticonvulsant), oxytocin (neuropeptide) and atomoxetine was insufficient for estimates of effectiveness.
AUTHORS' CONCLUSIONS
There is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N-acetylcysteine is weak, but these medications are also worth further investigation.
Topics: Acetylcysteine; Adult; Anticonvulsants; Antidepressive Agents; Buspirone; Dronabinol; Female; Humans; Male; Marijuana Abuse; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists; Selective Serotonin Reuptake Inhibitors; Young Adult
PubMed: 30687936
DOI: 10.1002/14651858.CD008940.pub3 -
Translational Andrology and Urology Aug 2016Delayed ejaculation (DE) is an uncommon and a challenging disorder to treat. It is often quite concerning to patients and it can affect psychosocial well-being. Here we... (Review)
Review
Delayed ejaculation (DE) is an uncommon and a challenging disorder to treat. It is often quite concerning to patients and it can affect psychosocial well-being. Here we reviewed how DE is treated pharmacologically .We also highlighted specific settings where drugs could be introduced to medical practice. Electronic databases were searched from 1966 to February 2016, including PubMed MEDLINE, EMBASE, EBCSO Academic Search Complete, Cochrane Systematic Reviews Database, and Google Scholar using key words; delayed ejaculation, retarded ejaculation, inhibited ejaculation, drugs, treatment, or pharmacology. To achieve the maximum sensitivity of the search strategy and to identify all studies, we combined "delayed ejaculation" as Medical Subject Headings (MeSH) terms or keywords with each of "testosterone" or "cabergoline" or "bupropion" or "amantadine" or "cyproheptadine" or "midodrine" or "imipramine" or "ephedrine" or "pseudoephedrine" or "yohimbine" or "buspirone" or "oxytocin" or "bethanechol" as MeSH terms or keywords. There are a number of drugs to treat patients with DE including: testosterone, cabergoline, bupropion, amantadine, cyproheptadine, midodrine, imipramine, ephedrine, pseudoephedrine, yohimbine, buspirone, oxytocin, and bethanechol. Although there are many pharmacological treatment options, the evidence is still limited to small trials, case series or case reports. Review of literature showed that evidence level 1 (Double blind randomized clinical trial) studies were performed with testosterone, oxytocin, buspirone or bethanechol treatment. It is concluded that successful drug treatment of DE is still in its infancy. The clinicians need to be aware of the pathogenesis of DE and the pharmacological basis underlying the use of different drugs to extend better care for these patients. Various drugs are available to address such problem, however their evidence of efficacy is still limited and their choice needs to be individualized to each specific case.
PubMed: 27652229
DOI: 10.21037/tau.2016.05.05