The Role of Glutamate in Anxiety and Related Disorders

CNS Spectrums ◽  
2005 ◽  
Vol 10 (10) ◽  
pp. 820-830 ◽  
Author(s):  
Bernadette M. Cortese ◽  
K. Luan Phan
Keyword(s):  
Anxiety Disorders ◽  
Metabotropic Glutamate Receptors ◽  
Selective Serotonin Reuptake Inhibitors ◽  
The United States ◽  
Current Treatment ◽  
Health Concern ◽  
Compulsive Disorder ◽  
Fear Potentiated Startle ◽  
Fear And Anxiety

AbstractAnxiety, stress, and trauma-related disorders are a major public health concern in the United States. Drugs that target the γ-aminobutyric acid or serotonergic system, such as benzodiazepines and selective serotonin reuptake inhibitors, respectively, are the most widely prescribed treatments for these disorders. However, the role of glutamate in anxiety disorders is becoming more recognized with the belief that drugs that modulate glutamatergic function through either ionotropic or metabotropic glutamate receptors have the potential to improve the current treatment of these severe and disabling illnesses. Animal models of fear and anxiety have provided a method to study the role of glutamate in anxiety. This research has demonstrated that drugs that alter glutamate transmission have potential anxiolytic action for many different paradigms including fear-potentiated startle, punished responding, and the elevated plus maze. Human clinical drug trials have demonstrated the efficacy of glutamatergic drugs for the treatment of obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, and social phobia. Recent data from magnetic resonance imaging studies provide an additional link between the glutamate system and anxiety. Collectively, the data suggest that future studies on the mechanism of and clinical efficacy of glutamatergic agents in anxiety disorders are appropriately warranted.

Efficacy of Combined Pharmacotherapy and Psychotherapy Versus Monotherapy in the Treatment of Anxiety Disorders

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S12) ◽  
pp. 29-33 ◽  
Author(s):  
Donald W. Black
Keyword(s):  
Anxiety Disorders ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Randomized Clinical Trials ◽  
Behavioral Therapy ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Empirical Support ◽  
The United States ◽  
Compulsive Disorder ◽  
Review Criteria

AbstractAnxiety disorders in the United States are prevalent, widespread, and disabling. These illnesses may account for almost one third of the $148 billion total mental health bill each year. Pharmacologic options include tricyclic antidepressants, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and anxiolytics. Psychological treatments include cognitive-behavioral therapy (CBT), cognitive therapy, exposure, and ritual prevention therapies. Despite insufficient evidence, many experts recommend combined treatment, generally medication with CBT. A literature review was conducted to examine studies with random assignment, adequate methods and sample sizes, blind assessments, sufficient dosages and durations of treatment, and satisfactory reporting of data, to determine whether combined treatment was superior to monotherapy. Twenty-six randomized clinical trials were identified; nine met review criteria. A review of relevant studies could not confirm the superiority of combined treatment over monotherapy. In one of four studies of obsessive-compulsive disorder, combined treatment produced better results than monotherapy.  There was no evidence of superiority for combined therapy over monotherapy for the treatment of social phobia or generalized anxiety disorder. There were no studies that met review criteria for either specific phobia or posttraumatic stress disorder (PTSD). With panic disorder, there was evidence that combined treatment might actually lead to worse outcome. Combined treatment is commonly recommended, but empirical support is limited. More research is needed. There are few well-designed studies, and little data regarding PTSD and specific phobias.

Ziprasidone as an Augmenting Agent in the Treatment of Anxiety-Spectrum Disorders

CNS Spectrums ◽  
2005 ◽  
Vol 10 (3) ◽  
pp. 176-179 ◽  
Author(s):  
Daniel L. Crane
Keyword(s):  
Anxiety Disorders ◽  
Selective Serotonin Reuptake Inhibitors ◽  
The United States ◽  
Pharmacologic Treatment ◽  
Obsessive Compulsive ◽  
Health Concerns ◽  
Compulsive Disorder ◽  
The Past ◽  
Augmentation Strategies ◽  
Spectrum Disorders

AbstractAnxiety disorders are currently one of the most common health concerns in the United States. Overall, they are the single largest cost to the healthcare system. They are also underdiagnosed and undertreated. Selective serotonin reuptake inhibitors and benzodiazepines appear to be the most common pharmacologic treatment approaches. Unfortunately, not all patients respond to these treatments. Many augmentation strategies have been tried in the past with varying levels of success or safety. This article describes a safe and highly effective augmentation technique in patients suffering from some of the most serious and debilitating forms of anxiety disorders, namely obsessive-compulsive disorder and panic disorder.

The interplay of genotype and environment in the development of fear and anxiety

e-Neuroforum ◽  
2013 ◽  
Vol 19 (3) ◽  
Author(s):  
N. Sachser ◽  
K.-P. Lesch
Keyword(s):  
Individual Differences ◽  
Environmental Factors ◽  
Anxiety Disorders ◽  
Candidate Gene ◽  
Early Development ◽  
Genetic Variants ◽  
External Influences ◽  
Postnatal Environment ◽  
Fear And Anxiety

AbstractIndividual differences in fear, anxiety, and the etiology of anxiety disorders develop dur­ing ontogeny. They are due to both genet­ic and environmental factors. With regard to the role of the environment, the organism is most susceptible to external influences dur­ing early development. Accordingly, stressors that impinge on the maternal organism dur­ing pregnancy evoke high levels of anxiety in the offspring later in life, as does an adverse early postnatal environment. However, anxi­ety-related circuits in the central nervous sys­tem retain their plasticity in adulthood, i.e., levels of anxiety can also be modified by ex­perience across the entire successive lifespan. Notably, the effects of external stressors on the individual’s level of anxiety are modulat­ed by genotype. Such genotype-by-environ­ment interactions are particularly well stud­ied in relation to genetic variants that modu­late the function of the serotonin transport­er. Thus, this review focuses on this candidate gene to elucidate the interplay of genotype and environment in the development of fear and anxiety.

New Therapies for Osteoporosis

2008 ◽  
Vol 22 (1) ◽  
pp. 53-64
Author(s):  
Karly A. Hegge ◽  
Anisa S. Fornoff ◽  
Sheryl L. Gutierres ◽  
Sally L. Haack
Keyword(s):  
Therapeutic Option ◽  
Sequential Therapy ◽  
The United States ◽  
Health Concern ◽  
Treatment Of Osteoporosis ◽  
Estrogen Receptor Modulators ◽  
Osteoporosis In Men ◽  
Surrogate Measures ◽  
Receptor Modulators

Osteoporosis is a growing health concern in the United States, with an enormous impact on morbidity and mortality. Despite published guidelines to aid clinicians in its management, several controversies remain. Many trials evaluate surrogate measures of bone strength rather than more clinically relevant outcomes, including fracture. Furthermore, the role of combination and sequential therapy remains unclear. Limited data are available regarding appropriate duration of therapy, management of osteoporosis in men, and treatment of glucocorticoid-induced osteoporosis. The development of unique therapeutic agents could potentially revolutionize the treatment of osteoporosis. Once yearly zoledronic acid may provide advantages over existing therapies. Because of limitations with existing selective estrogen receptor modulators, the search for agents with better efficacy and safety profiles has led to the development of several new medications within this class. Finally, denosumab, a monoclonal antibody to receptor activator for nuclear factor-kappa B ligand, also represents a novel therapeutic option for osteoporosis.

Role of serotonin in obsessive-compulsive disorder

1998 ◽  
Vol 173 (S35) ◽  
pp. 13-20 ◽  
Author(s):  
H. G. Baumgarten ◽  
Z. Grozdanovic
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Expression Patterns ◽  
Term Treatment ◽  
Continuous Treatment ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Long Term Treatment ◽  
Pre Treatment

Background Serotonin may play a role in the pathophysiology of obsessive-compulsive disorder (OCD) because of the anti-obsessional effect of selective serotonin reuptake inhibitors (SSRJs).Method The literature is reviewed on knowledge of the role of serotonergic neurons in brain function, studies on monoamine metabolites in cerebrospinal fluid (CSF), various stress neuropeptides, neuroendocrine and behavioural challenge after administration of direct and indirect serotomimetic compounds, and neuroanatomical data on brain circuits organising behaviour.Results In most of the OCD cases analysed, CSF 5-hydroxyindoleacetic acid and homovanillic acid concentrations do not significantly differ from age-corrected controls. However, a relationship appears to exist between pre-treatment levels of these metabolites and clinical response to drugs acting on the serotonin transporter. Abnormalities in CSF arginine vasopressin, corticotropin-releasing hormone, oxytocin and somatostatin levels have been reported in OCD. Long-term treatment with high-doses of clomipramine, fluvoxamine, and fluoxetine tend to correct these neuropeptide abnormalities.Conclusions We hypothesise that continuous treatment with SSRJs alters serotonin turnover and neuropeptide expression patterns in OCD-entertaining functional forebrain/midbrain circuits.

Cognitive-Behavioral Therapy and Integrated Approaches in the Treatment of Obsessive-Compulsive Disorder

CNS Spectrums ◽  
1999 ◽  
Vol 4 (S3) ◽  
pp. 35-40 ◽  
Author(s):  
Fritz Hohagen
Keyword(s):  
Cognitive Behavioral Therapy ◽  
Obsessive Compulsive Disorder ◽  
Behavior Therapy ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Behavioral Therapy ◽  
Cognitive Behavioral ◽  
Mental Condition ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

AbstractObsessive-compulsive disorder (OCD) has long been considered a treatment-refractory mental condition. Neither pharmacologic nor psychodynamic therapy has been proven to treat OCD effectively. Yet the prognosis for OCD has changed dramatically in recent years with the introduction of behavior therapy and the use of selective serotonin reuptake inhibitors (SSRIs). Many studies have shown that behavior therapy, especially exposure with response prevention, and SSRIs reduce obsessive-compulsive symptoms significantly. Still, many unanswered questions—including the role of cognitive therapy in the treatment of OCD, exposure therapy vs multimodal behavioral therapy, individual versus group therapy, outcome predictors in adults, adolescents, and children, and the role of combination treatment using an SSRI and cognitive-behavioral therapy—remain. This article will explore these issues as well as suggest directions for further research into OCD.

The Role of Biomaterials in Insulin Delivery Systems

1980 ◽  
Vol 3 (5) ◽  
pp. 299-304 ◽  
Author(s):  
S.D. Bruck
Keyword(s):  
Blood Glucose ◽  
Glucose Sensor ◽  
Insulin Delivery ◽  
The United States ◽  
Delivery Systems ◽  
Open Loop ◽  
Health Concern ◽  
Glucose Levels ◽  
Blood Glucose Levels

The control of blood glucose levels in diabetes involving devices are critically reviewed, and the role of blood-contacting biomaterial components analyzed. These include mechanical insulin-delivery systems of the closed-loop type that require an electronic glucose sensor and feedback, and open-loop systems that deliver insulin without a sensor and feedback. Whole pancreatic and islet transplantations, islet encapsulation, and the potential role of polymeric sustained drug delivery systems are discussed. The medical and social impacts of diabetes mellitus are of prime public health concern and of even greater magnitude than those of heart disease in the United States. While future advances in device design, miniaturization, and biometrials technology will significantly add to the arsenal of therapeutic alternatives, devices capable of controlling blood glucose levels ought to be viewed as mere interim phases rather than as final goals of the problem.

scholarly journals Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options

2020 ◽  
Vol 11 ◽  
Author(s):  
Amir Garakani ◽  
James W. Murrough ◽  
Rafael C. Freire ◽  
Robyn P. Thom ◽  
Kaitlyn Larkin ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Anxiety Disorder ◽  
Anxiety Disorders ◽  
Posttraumatic Stress ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Stress Disorder ◽  
Controlled Trials ◽  
Beta Adrenergic ◽  
Adrenergic Agents ◽  
Compulsive Disorder

Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebo- controlled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.

scholarly journals Role of Glutamatergic System in Obsessive-Compulsive Disorder with Possible Therapeutic Implications

2017 ◽  
Vol 51 (06) ◽  
pp. 229-242 ◽  
Author(s):  
Přemysl Vlček ◽  
Jakub Polák ◽  
Martin Brunovský ◽  
Jiří Horáček
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Brain Regions ◽  
Glutamatergic System ◽  
Obsessive Compulsive ◽  
Therapeutic Implications ◽  
Temporal Lobes ◽  
Compulsive Disorder ◽  
Neuropsychological Evidence

AbstractObsessive-compulsive disorder (OCD) is a chronic psychiatric illness and 1 of the most common anxiety disorders with the prevalence of 3%. Although its pathogenesis remains unclear, the traditional model focused on alternations in the serotonin system. Selective serotonin reuptake inhibitors provide the most effective treatment; however, as much as 40–60% of patients do not respond to antidepressants therapy. Thus, attention has shifted towards other neurotransmitter systems and related neuroanatomical structures. Recently, there is extensive evidence showing a key role of glutamate pathways abnormalities within the cortico-striatal-thalamo-cortical circuitry and temporal lobes in OCD pathogenesis. In this review, we link together the existent neuroanatomical, neurophysiological, and neuropsychological evidence to argue for potential benefits of adjuvant treatment with glutamatergic agents, especially memantine. By a targeted de-excitation effect on the glutamatergic system in the temporal lobes and connected brain regions, memantine might further alleviate OCD symptoms. This effect should be even more pronounced in certain subtypes of patients with specific cognitive deficits and maladaptive compensatory memory processes (e.g., checkers).

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