Review

Authors: Borwin Bandelow, Sophie Michaelis, Dirk Wedekind...

Anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, social anxiety disorder, and others) are the most prevalent psychiatric disorders, and are associated with a high burden of illness. Anxiety disorders are often underrecognized and undertreated in primary care. Treatment is indicated when a patient shows marked distress or suffers from complications resulting from the disorder. The treatment recommendations given in this article are based on guidelines, meta-analyses, and systematic reviews of randomized controlled studies. Anxiety disorders should be treated with psychological therapy, pharmacotherapy, or a combination of both. Cognitive behavioral therapy can be regarded as the psychotherapy with the highest level of evidence. First-line drugs are the selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Benzodiazepines are not recommended for routine use. Other treatment options include pregabalin, tricyclic antidepressants, buspirone, moclobemide, and others. After remission, medications should be continued for 6 to 12 months. When developing a treatment plan, efficacy, adverse effects, interactions, costs, and the preference of the patient should be considered.

Topics: Anti-Anxiety Agents; Anxiety Disorders; Benzodiazepines; Cognitive Behavioral Therapy; Humans; Psychotherapy; Selective Serotonin Reuptake Inhibitors

PubMed: 28867934
DOI: 10.31887/DCNS.2017.19.2/bbandelow

Review

Authors: Víctor Ruggieri

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

Review

Authors: Amir Garakani, James W Murrough, Rafael C Freire...

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.

PubMed: 33424664
DOI: 10.3389/fpsyt.2020.595584

Review

Authors: Aneesh K Mishra, Anuj R Varma

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

Review

Authors: Madhusudan Grover, Gianrico Farrugia, Vincenzo Stanghellini...

Gastroparesis is defined by delayed gastric emptying (GE) and symptoms of nausea, vomiting, bloating, postprandial fullness, early satiety and abdominal pain. Most common aetiologies include diabetes, postsurgical and postinfectious, but in many cases it is idiopathic. Clinical presentation and natural history vary by the aetiology. There is significant morbidity and healthcare utilisation associated with gastroparesis. Mechanistic studies from diabetic animal models of delayed GE as well as human full-thickness biopsies have significantly advanced our understanding of this disorder. An innate immune dysregulation and injury to the interstitial cells of Cajal and other components of the enteric nervous system through paracrine and oxidative stress mediators is likely central to the pathogenesis of gastroparesis. Scintigraphy and C breath testing provide the most validated assessment of GE. The stagnant gastroparesis therapeutic landscape is likely to soon see significant changes. Relatively newer treatment strategies include antiemetics (aprepitant), prokinetics (prucalopride, relamorelin) and fundic relaxants (acotiamide, buspirone). Endoscopic pyloromyotomy appears promising over the short term, especially for symptoms of nausea and vomiting. Further controlled trials and identification of the appropriate subgroup with pyloric dysfunction and assessment of long-term outcomes are essential. This review highlights the clinical presentation, diagnosis, mechanisms and treatment advancements for gastroparesis.

Topics: Endoscopy, Gastrointestinal; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans

PubMed: 31563877
DOI: 10.1136/gutjnl-2019-318712

Review

Authors: Jeffrey R Strawn, Laura Geracioti, Neil Rajdev...

Generalized anxiety disorder (GAD) often begins during adolescence or early adulthood and persists throughout the lifespan. Randomized controlled trials support the efficacy of selective serotonin and selective serotonin norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively), as well as benzodiazepines, azapirones, anti-adrenergic medications, melatonin analogs, second-generation antipsychotics, kava, and lavender oil in GAD. However, psychopharmacologic treatment selection requires clinicians to consider multiple factors, including age, co-morbidity, and prior treatment. Areas covered: The authors review the literature concerning pharmacotherapy for pediatric and adult patients with GAD with specific commentary on the efficacy and tolerability of selected agents in these age groups. The authors describe an algorithmic approach to the pediatric and adult patient with GAD and highlight considerations for the use of selected medications in these patients. Expert opinion: In adults with GAD, SSRIs and SNRIs represent the first-line psychopharmacologic treatment while second-line pharmacotherapies include buspirone, benzodiazepines, SGAs, and pregabalin. In pediatric patients with GAD, SSRIs should be considered the first line pharmacotherapy and psychotherapy enhances antidepressant response.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Child; Evidence-Based Practice; Humans; Monoamine Oxidase Inhibitors; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors

PubMed: 30056792
DOI: 10.1080/14656566.2018.1491966

Review

Authors: Andrew R Garrett, Jason S Hawley

PURPOSE OF REVIEW

Antidepressant-associated movement disorders are a well-described phenomenon. However, antidepressant-associated bruxism, jaw pain, or jaw spasm, while reported in dental literature, is less commonly recognized among neurologists. We summarize the clinical features and treatment of antidepressant-associated bruxism and associated jaw pain through a systematic review of case reports.

RECENT FINDINGS

Antidepressant-associated bruxism may occur in pediatric and adult patients, most commonly among female patients. Patients may develop symptoms with short-term and long-term antidepressant use. Fluoxetine, sertraline, and venlafaxine were the most commonly reported offending agents. Symptoms may begin within 3-4 weeks of medication initiation and may resolve within 3-4 weeks of drug discontinuation, addition of buspirone, or substitution with another pharmacologic agent. The incidence of this phenomenon is unknown.

SUMMARY

Bruxism associated with antidepressant use is an underrecognized phenomenon among neurologists, and may be treated with the addition of buspirone, dose modification, or medication discontinuation.

PubMed: 29708207
DOI: 10.1212/CPJ.0000000000000433

Review

Authors: Roueen Rafeyan, George I Papakostas, W Clay Jackson...

​​​​ About 30%-50% of patients experience inadequate response to antidepressant therapy, and treatment choices for these patients include augmenting the antidepressant with another therapy, increasing the dose, switching to a different antidepressant, or combining antidepressants. Clinicians should tailor treatment strategies based on patients' response, tolerability, and disease severity. In this activity, augmentation and adjunctive strategies involving atypical antipsychotics, as well as off-label options including buspirone, stimulants, thyroid hormone, and lithium, are reviewed.​ ​.

Topics: Antidepressive Agents; Depressive Disorder, Major; Drug Substitution; Humans; Psychiatric Status Rating Scales; Treatment Failure

PubMed: 32412697
DOI: 10.4088/JCP.OT19037BR3

Meta-Analysis Review

Authors: Lone Baandrup, Bjørn H Ebdrup, Jesper Ø Rasmussen...

BACKGROUND

Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the general population, with increased prevalence in psychiatric populations and the elderly. After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence. This review investigated if pharmacological interventions can facilitate benzodiazepine tapering.

OBJECTIVES

To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use.

SEARCH METHODS

We searched the following electronic databases up to October 2017: Cochrane Drugs and Alcohol Group's Specialised Register of Trials, CENTRAL, PubMed, Embase, CINAHL, and ISI Web of Science. We also searched ClinicalTrials.gov, the WHO ICTRP, and ISRCTN registry, and checked the reference lists of included studies for further references to relevant randomised controlled trials.

SELECTION CRITERIA

We included randomised controlled trials comparing pharmacological treatment versus placebo or no intervention or versus another pharmacological intervention in adults who had been treated with benzodiazepines for at least two months and/or fulfilled criteria for benzodiazepine dependence (any criteria).

DATA COLLECTION AND ANALYSIS

We used standard methodological procedures expected by Cochrane.

MAIN RESULTS

We included 38 trials (involving 2543 participants), but we could only extract data from 35 trials with 2295 participants. Many different interventions were studied, and no single intervention was assessed in more than four trials. We extracted data on 18 different comparisons. The risk of bias was high in all trials but one. Trial Sequential Analysis showed imprecision for all comparisons.For benzodiazepine discontinuation, we found a potential benefit of valproate at end of intervention (1 study, 27 participants; risk ratio (RR) 2.55, 95% confidence interval (CI) 1.08 to 6.03; very low-quality evidence) and of tricyclic antidepressants at longest follow-up (1 study, 47 participants; RR 2.20, 95% CI 1.27 to 3.82; low-quality evidence).We found potentially positive effects on benzodiazepine withdrawal symptoms of pregabalin (1 study, 106 participants; mean difference (MD) -3.10 points, 95% CI -3.51 to -2.69; very low-quality evidence), captodiame (1 study, 81 participants; MD -1.00 points, 95% CI -1.13 to -0.87; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -3.57 points, 95% CI -5.34 to -1.80; very low-quality evidence), tricyclic antidepressants (1 study, 38 participants; MD -19.78 points, 95% CI -20.25 to -19.31; very low-quality evidence), and flumazenil (3 studies, 58 participants; standardised mean difference -0.95, 95% CI -1.71 to -0.19; very low-quality evidence) at end of intervention. However, the positive effect of paroxetine on benzodiazepine withdrawal symptoms did not persist until longest follow-up (1 study, 54 participants; MD -0.13 points, 95% CI -4.03 to 3.77; very low-quality evidence).The following pharmacological interventions reduced symptoms of anxiety at end of intervention: carbamazepine (1 study, 36 participants; MD -6.00 points, 95% CI -9.58 to -2.42; very low-quality evidence), pregabalin (1 study, 106 participants; MD -4.80 points, 95% CI -5.28 to -4.32; very low-quality evidence), captodiame (1 study, 81 participants; MD -5.70 points, 95% CI -6.05 to -5.35; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -6.75 points, 95% CI -9.64 to -3.86; very low-quality evidence), and flumazenil (1 study, 18 participants; MD -1.30 points, 95% CI -2.28 to -0.32; very low-quality evidence).Two pharmacological treatments seemed to reduce the proportion of participants that relapsed to benzodiazepine use: valproate (1 study, 27 participants; RR 0.31, 95% CI 0.11 to 0.90; very low-quality evidence) and cyamemazine (1 study, 124 participants; RR 0.33, 95% CI 0.14 to 0.78; very low-quality evidence). Alpidem decreased the proportion of participants with benzodiazepine discontinuation (1 study, 25 participants; RR 0.41, 95% CI 0.17 to 0.99; number needed to treat for an additional harmful outcome (NNTH) 2.3 participants; low-quality evidence) and increased the occurrence of withdrawal syndrome (1 study, 145 participants; RR 4.86, 95% CI 1.12 to 21.14; NNTH 5.9 participants; low-quality evidence). Likewise, magnesium aspartate decreased the proportion of participants discontinuing benzodiazepines (1 study, 144 participants; RR 0.80, 95% CI 0.66 to 0.96; NNTH 5.8; very low-quality evidence).Generally, adverse events were insufficiently reported. Specifically, one of the flumazenil trials was discontinued due to severe panic reactions.

AUTHORS' CONCLUSIONS

Given the low or very low quality of the evidence for the reported outcomes, and the small number of trials identified with a limited number of participants for each comparison, it is not possible to draw firm conclusions regarding pharmacological interventions to facilitate benzodiazepine discontinuation in chronic benzodiazepine users. Due to poor reporting, adverse events could not be reliably assessed across trials. More randomised controlled trials are required with less risk of systematic errors ('bias') and of random errors ('play of chance') and better and full reporting of patient-centred and long-term clinical outcomes. Such trials ought to be conducted independently of industry involvement.

Topics: Adult; Antidepressive Agents; Aspartic Acid; Benzodiazepines; Buspirone; Carbamazepine; Ethylamines; Flumazenil; Homeopathy; Humans; Imidazoles; Lithium Compounds; Melatonin; Paroxetine; Pregabalin; Progesterone; Pyridines; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Sulfides; Withholding Treatment

PubMed: 29543325
DOI: 10.1002/14651858.CD011481.pub2