Anxiety Disorders
INTRODUCTION
Population
Anxiety disorders affect almost one out of every five people in the United States each year. Worry and uncertainty are common symptoms of many ailments, lasting for six months or more and interfering with daily activities. Anxiety disorders might put you at risk for additional health problems such as heart disease, diabetes, drug and alcohol misuse, and depression. (Knowles & Olatunji, 2020). The majority of anxiety disorders improve with therapy. The treatment plan determines the type of anxiety disorder.
In most cases, medications, psychotherapy, or a combination of the two are beneficial in reducing distressing symptoms. Most people with anxiety disorders are treated; patients with anxiety are not vastly understood, making it challenging to help them back to total health. One of the most common types of anxiety illness is a social anxiety disorder, also known as social phobia. It affects roughly 15 million adults in the United States, equally impacting men and women. If not treated, social phobia can last for years, if not a lifetime. People with social phobia may feel uncomfortable for days or weeks before attending a social event. They’re typically embarrassed, self-conscious and scared of being evaluated. They have a hard time communicating with others.
Another prominent type of anxiety illness is a generalized anxiety disorder, which affects over 7 million individuals in the United States, and panic disorder, which affects about 6 million. (Sapra et al., 2020). Both are twice as prevalent in women as they are in men. People with generalized anxiety disorder obsess over trivial matters such as health, money, and family difficulties, even when they know, there’s no reason to be concerned. They are quickly startled, unable to relax, and unable to concentrate. They have trouble falling asleep and staying asleep. Headaches, muscle aches, and inexplicable symptoms are all possibilities. When you’re under a lot of stress, your symptoms worsen.
Panic disorder causes people to have sudden, repeated bursts of fear, known as panic attacks, which last several minutes or longer. They may feel as if they can’t breathe or suffer a heart attack during a panic episode. They may be afraid of losing control or experience a sense of disconnection from reality. Panic disorder is not associated with all people having panic attacks. If the episodes are frequent and you’re frightened of getting another one at any moment, you probably have panic disorder. Anxiety disorders are often passed down the generations. However, scientists are baffled as to why some family members have diseases and others do not. Anxiety disorders are caused by no specific genes that have been discovered. (Gambin et al., 2021). The brain connections of individuals who responded best after three months of CBT were similar in 38 adults with social phobia. Compared to a clinician’s assessment alone, this brain analysis resulted in a significant improvement in predicting treatment response. More considerable research is required to confirm the approach’s benefits.
TYPES OF ANXIETY DISORDERS
Anxiety disorders include generalized anxiety disorder (gad), phobias, panic disorder, and separation anxiety, to name a few.
Generalized anxiety disorder (GAD).
Although generalized anxiety disorder shares symptoms with panic disorder, obsessive-compulsive disorder, and other forms of anxiety, they are all distinct disorders. Living with a generalized anxiety disorder for a long time might be challenging. (Toussaint et al., 2020). It’s common for it to occur in the context of other anxiety or mood disorders. Psychotherapy and medication can treat generalized anxiety disorder with psychotherapy or medication. Changing your way of living, learning coping skills, and practicing relaxation techniques can benefit you.
Symptoms
Symptoms of generalized anxiety disorders can vary. It means that the patient may not experience all symptoms at once, and they may not manifest chronologically. These symptoms include worry or anxiety over various issues out of proportion to the severity of the occurrence—overthinking plans and solutions to account for all possible worst-case scenarios (Huang & Zhao2020)—perceiving events and situations as dangerous, even when they aren’t. Uncertainty is difficult to deal with. Fear of making the wrong decision and indecisiveness. Inability to put one worry aside or let go of it. Inability to relax, restlessness, and a tense or tense feeling. Concentration problems.
PHOBIAS
A phobia is an anxiety condition in which a person has an intense, illogical dread of a scenario, live being, place, or item. When someone has a phobia, they will frequently shape their lives to avoid situations that they perceive to be harmful. The perceived threat outweighs any threat offered by the terror source (Eaton et al., 2018). There are three types of phobias: specific phobia, which is brought about by an irrational, intense fear of a particular trigger. Social phobia, a different kind of phobia, is brought about by one’s fear of humiliation or being singled out through social interactions. Agoraphobia, on the other hand, is brought about by fear of being dominated, meaning that one fears that they may not have the ability to escape certain situations.
Symptoms
Phobias share most symptoms with other types of anxiety, including the inability to function normally when exposed to the trigger, recognition that the fear is irrational, unreasonable, and exaggerated, and a failure to control the feelings.
INTERVENTIONS
PHARMACOLOGICAL INTERVENTION
Anxiety disorders are being treated with pharmaceutical medications that are safer and more bearable than they were 30 years ago. Despite a better understanding of the pathophysiology of anxiety, therapy efficacy and duration have not increased in most patients. Furthermore, despite billions of dollars spent on drug development, novel medicines have yet to reach the market (Carl et al., 2020). In examining the literature on existing treatments, there is a proposal that a better study on the causes of incomplete treatment response and the comparative efficacy of medication combinations and sequencing would help evidence-based management. Despite these remarkable improvements, between one-third and half of the patients using a modern antidepressant do not receive long-term anxiety relief.
Even though patients frequently use antidepressant medications for years, there is a lack of high-quality data on the treatments’ long-term efficacy. The problem is exacerbated by the expanding number of drug classes, which has led to clinicians combining pharmaceuticals and changing dose regimens in the absence of reliable data on the best therapy combinations. To understand the effectiveness of this intervention, we have to understand the safety, efficiency, and tolerability of first and second-hand line drugs dealing with anxiety disorders and understanding the evidence of the use of drug-drug and drug–psychotherapy combinations as supplementary or augmenting therapeutic options for anxiety that has resisted treatment. We examine future innovations in the treatment of anxiety disorders in the remainder of this paper, including novel molecular targets, memory-modulating medicines, and psychedelic and narcotic medications. Although the results are not incredibly encouraging, there are concrete questions that can only be answered through extensive research.
Antidepressant medications
The SSRIs, and to a lesser extent, the SNRIs, are the most thoroughly investigated pharmacological therapies for anxiety disorders. The only exception is a specific phobia. Because exposure therapy is considered the first-line treatment for specific phobias, these drugs have rarely been investigated or utilized clinically. The few studies that have compared SNRIs to SSRIs have found similar results. SSRIs and SNRIs boost synaptic levels of 5-HT in the synapse by preventing the reuptake of serotonin or norepinephrine, respectively (Boschloo et al. 2019). This sets off a chain reaction involving other neurotransmitters, second messengers, and early genes, resulting in long-term neurochemical alterations in the brain. SSRIs are helpful for a wide range of psychiatric conditions, have few adverse effects, and have a limited abuse potential; they are also similarly effective, safer in overdose, and more acceptable than earlier tricyclic antidepressants.
The most common moderate and temporary adverse effects are nausea, diarrhea, headache, sleeplessness, jitteriness, or restlessness, which affect 30–50% of patients. Although this has not been proven, it is assumed that nervous patients are more vulnerable to jitteriness when using these agents. These side effects can be reduced by starting with a low dose and gradually increasing it over 2–4 weeks. Sexual side effects include decreased sexual desire, performance, or satisfaction are prevalent, affecting one-third to half of SSRI patients. Various drugs can help erectile dysfunction and anorgasmia, but lowered sexual interest is more difficult to cure and is often better managed with dose reductions or drug breaks. Finally, SSRIs can interact metabolically with other medicines, altering blood levels, and are linked to a withdrawal syndrome that might mirror anxiety when stopped abruptly.
Benzodiazepines
By acting on a chloride ion channel, benzodiazepines bind to a specific receptor location on the gamma-aminobutyric acid–A receptor complex and promote GABA inhibitory actions. They were once regarded as first-line therapies for anxiety because of their tolerance and efficacy on par with TCAs. Still, they were demoted to second-line status when it became evident that SSRIs were both more tolerant and effective. Benzodiazepines are currently used mainly for people who have had poor results with antidepressants. Benzodiazepines are also utilized for their powerful, short-term effects or to help lower anxiety during the first weeks of treatment with an antidepressant, when anxiolytic benefits have not yet manifested (Agarwal & Landon, 2019). These applications are tempting to patients, but they are not necessarily ideal because they can boost drug intake, act as a safety signal that undermines self-efficacy, and become ingrained in the conditioned fear response.
When benzodiazepines are taken on a needed basis, these problems are amplified. As-needed use links pills to a rapid decrease in anxiety, thus rewarding avoidance of anxiety-provoking events and fostering longer-term drug addiction.
Chronic benzodiazepine use is linked to physiological dependence, short-term cognitive and psychomotor impairment, and withdrawal anxiety. Benzodiazepines are more likely to be abused by patients who have a history of substance abuse. Benzodiazepines can be gradually tapered and removed over several months if clinically required while commencing another medicine or CBT.
Alpha-Delta calcium channel anticonvulsants
Gabapentin and the newer drug pregabalin belong to the alpha–delta calcium channel class of anticonvulsants, which diminish neuronal excitability and are similar to benzodiazepines in their capacity to change the balance between inhibitory and excitatory neuronal activity (Yadav et al., 2019). These medicines, like benzodiazepines, have a quick onset of effect and outperform placebo in GAD and SAD. According to a meta-analysis, pregabalin may even help those with GAD who have depressive symptoms. These medications have fewer misuse, tolerance, and withdrawal issues than benzodiazepines and have been used to treat both alcohol and amphetamine addiction.
Approach to non-initial response
Many patients who suffer from anxiety disorders do not react to treatment completely. Prescribers frequently mix an antidepressant with an effective anxiolytic medicine with a different mechanism of action, such as benzodiazepine or other antidepressants, at this stage (Craske et al., 2019). Typically, if symptoms do not improve by 25% after six weeks, they will move to a new agent, and if symptoms do not resolve within 12 weeks, they will add a new agent. Another method, known as “augmentation,” involves adding a medication that isn’t known to be successful on its own but improves the reaction to the other drug. Only a few studies have been scientifically investigated with the efficacy of combination or augmentation techniques in anxiety disorders. Large sample sizes are required for this research.
Pharmacotherapy in combination with psychotherapy
Patients with anxiety disorders prefer psychotherapy to psychotropic interventions, yet psychotropic medications are more likely to be prescribed initially. There has been some interest in combining cognitive-behavioral therapies with antidepressants or benzodiazepines, but this strategy has not generated notable additive effects. These findings have prompted some researchers to conclude that combination treatment should not be regarded as a first-line therapeutic option and should instead be reserved for people who require medication for severe anxiety. However, limited evidence suggests that combining medicine with CBT or CBT with drugs in patients with refractory anxiety disorders is ineffective.
ANTIDEPRESSANTS
Antidepressants and anxiolytics function by changing the balance of neurotransmitters, which are molecules found in the brain. The physical symptoms accompanying an anxiety attack are treated with beta-blockers and other medications. Because they have a sedative effect, first-generation antihistamines are also used to help with anxiety symptoms (Dunlop et al., 2019). Anxiety disorders are linked to chemical anomalies in the brain affecting neurotransmitters including serotonin, norepinephrine, GABA, or gamma-aminobutyric acid. These substances are connected to a person’s feeling of well-being or ability to relax.
BETA-BLOCKERS AND AZAPIRONES
Beta-blockers and azapirones are less commonly prescribed. Beta-blockers are used as single-dose medicines for performance-related anxiety because they can diminish the peripheral physical symptoms of anxiety in 30–60 minutes. Still, they do not affect the cognitive and emotional symptoms of anxiety (Holla & Arivazhahan, 2021). Azapirones bind to the 5-HT1A receptor and are thought to affect serotonin neuron firing rate control. They usually take 2–4 weeks to take action, are well tolerated, and do not have the same side effects as benzodiazepines. On the other hand, GAD is the only anxiety disease in which azapirones have consistently shown benefit. Antidepressant medicines are the more reasonable therapy option for GAD because it frequently involves a depressive component.
APPLICATION OF ANXIETY MEDICATIONS
Panic disorder, obsessive-compulsive disorder, social anxiety disorder, general anxiety disorder, and post-traumatic stress disorder are all treated with antidepressants known as selective serotonin reuptake inhibitors. Panic disorder, post-traumatic stress disorder, and public anxiety disorder are treated with tricyclic antidepressants. Clomipramine, a tricyclic, can be used to treat obsessive-compulsive disorder (Turner et al., 2018). Panic disorder, social anxiety disorder, and post-traumatic stress disorder are treated with monoamine oxidase inhibitors antidepressants. Panic disorder, obsessive-compulsive disorder, social anxiety disorder, general anxiety disorder, and post-traumatic stress disorder are all treated with antidepressants, including serotonin-norepinephrine reuptake inhibitors.
The anti-anxiety drug buspirone is used to treat general anxiety disorder. Public anxiety disorder, social anxiety disorder, and panic disorder are all treated with benzodiazepines. General anxiety disorder can be treated with first-generation antihistamines like diphenhydramine.
COMPARISON OF INTERVENTIONS
Most people seeking care in clinical settings have GAD, PDA, or SAD. When symptoms are mild, temporary, and have no related social or occupational function impairment, not all anxiety disorders require treatment. However, treatment is necessary if a patient is in severe discomfort or is experiencing implications of the condition. Anxiety disorders are generally treated as outpatient procedures (Holla & Arivazhahan, 2021). Suicide, unresponsiveness to traditional therapies, or relevant comorbidities, such as severe depression, personality disorders, or substance misuse, are all reasons for hospitalization. Patients with various anxiety disorders show varying levels of healthcare use. For example, in the United States, 54.4 percent of patients with PDA visited health care facilities in a year, compared to only 27.3 percent of patients with particular phobias. Patients with PDA frequently believe they suffer from a severe bodily condition, such as a myocardial infarction, and require immediate medical attention. Still, persons with basic phobias think they can cope with the disorder.
There is evidence that anxiety disorders are undertreated significantly. Only 20.6 percent of people with anxiety sought professional care in an extensive European study. 23.2 percent of individuals who sought medical help received no treatment at all, 19.6 percent received only psychological treatment, 30.8 percent received only drug treatment, and 26.5 percent received both drug and psychotherapy treatment. Similarly, Dutch primary care research found that just 27% of patients with anxiety disorders received treatment based on guidelines. Patients should be educated on their diagnosis, the etiology, and the mechanisms of action of the various therapy options. Psychotherapy, pharmacotherapy, and other interventions should be included in the treatment plan after careful consideration of individual factors such as the patient’s preferences, previous treatment attempts, illness severity, comorbidities such as personality disorders, suicidal thoughts, local availability of treatment methods, wait time for psychotherapy appointments, costs, and other considerations.
PHARMACOTHERAPY
Anxiety and mood problems are quite frequent and can be extremely severe. Depression alone affects 350 million people globally, is a leading cause of suicide, and is one of the most debilitating illnesses. There has been a lot of research done on how to treat or manage the symptoms of mood and anxiety disorders. For example, pharmacotherapy and specialized types of counseling have been proven to be effective treatments. Other management options, in addition to medicines, can help people with mood and anxiety disorders reduce their symptoms by changing their lifestyles. Exercising and quitting smoking are two complementary strategies that are both beneficial (Carl et al., 2020). Many drugs demand a reduction in alcohol usage, which is likely causal, and alcohol problems are related to mood or anxiety disorders. Finally, data suggest that substance abuse issues can exacerbate mood or anxiety disorders.
Treatments and management techniques are not differentiated in the current clinical practice recommendations for severe depression. The American Psychiatric Association’s and the National Institute for Health and Care Excellence’s guidelines for treating depression emphasize pharmaceutical and psychosocial approaches and use the term management. Guidelines from the Royal Australian and New Zealand College of Psychiatrists, the Canadian “CANMAT” Guidelines, and the Scottish Intercollegiate Guidelines Network refer to techniques like exercise and quitting smoking as therapies while simultaneously using the term management. There is currently insufficient information about suggestions and treatments received, particularly in general population samples. The evidence on the amount to which people are recommended and receive various therapies and implement multiple management measures are varied.
Many studies assessing adherence to clinical prescriptions, on the other hand, reveal that many people are given suggestions and treated in ways that are often consistent with guidelines. However, most of the research analyzed used small or non-representative samples, and these studies tended to focus on the application of policies rather than actual management. Some research was carried out many years ago, and their findings may no longer be valid. As a result, there is limited research on how suggestions are not followed up on after they are made. This is referred to as a recommendation-implementation gap. Anecdotal and experimental data support this theory.
Recommendations have a solid tendency to influence people’s behavior and be implemented. Treatments, on the other hand, are frequently under-recommended. Almost all therapies or management techniques were proposed to less than 65 percent of the relevant population, except medicine. Only a tiny percentage of recommendations are carried out. This is evidence of a gap between recommendations and execution. However, the intensity of the effect varies significantly amongst therapies. The findings show that many people consider treatment or management techniques without seeking advice.
EFFECTIVENESS OF PHARMACOLOGICAL INTERVENTIONS IN ANXIETY
Over the last half-century, pharmacological therapies for anxiety disorders have gotten more acceptable, accessible, and numerous. Simultaneously, research has resulted in a far better knowledge of the neurological and physiological mechanisms behind persistent anxiety and stress reactions, pointing to novel therapeutic options for anxiety disorders. Despite these remarkable improvements, between one-third and half of the patients using a modern antidepressant do not receive long-term anxiety relief (Slee et al., 2019). Although patients frequently use antidepressant medications for years, there is a scarcity of high-quality data on the treatments’ long-term efficacy. The problem is exacerbated by the expanding number of drug classes, which has led to clinicians combining pharmaceuticals and changing dose regimens in the absence of reliable data on the best therapy combinations.
While much of pharmacological development focuses on improving the efficacy and tolerability of existing anxiety medications, considerable resources have been invested in finding novel molecular targets over the last decade. Recent research in this sector has focused on drugs that function more selectively on specific subtypes of serotonergic receptors. If pharmacological regulation of learning and memory could be demonstrated as a safe, reliable, and clear therapy strategy, it would be a huge step forward in translational science. For the time being, such potential remains hypothetical since more focused research is needed to address several conceptual, empirical, practical, and ethical challenges.
Memory consolidation is a well-known phenomenon, but memory reconsolidation is not. Side effects, delayed consolidation, and extinction must all be ruled out as potential explanations of apparent reconsolidation effects in numerous studies. Second, drugs that improve long-term consolidation may affect non-emotional memory and memory for events that occur before or after the target event. Today, patients with anxiety disorders benefit from decades of psychopharmacological research, which has resulted in side-effect profiles that are safer and more tolerable than before, but no change in efficacy. As we’ve seen, first-line antidepressants like SSRIs and perhaps SNRIs do an excellent job of decreasing anxiety, but they work slowly and don’t always lead to long-term remission. When a patient’s response is incomplete, physicians and patients must determine how to proceed with treatment.
New pharmacological therapies for anxiety are being developed in two directions: ongoing medication development focusing on highly selective neuroreceptor targets and pharmacological memory modulation to improve adaptive processes and hinder maladaptive strategies. Unfortunately, none of these therapy options are ready for widespread clinical application. For example, translational research has revealed drugs that act on particular molecular targets, but their efficacy and safety in animal models have seldom translated to people. Even if there are promising discoveries, drug companies may find that spending substantially in this field is not cost-effective because other medical disease applications may deliver a superior return on investment. (Slee et al., 2019). The subject of pharmacological memory and learning modification is still very fresh and intriguing. According to the study, such manipulation is not only theoretically but also empirically possible. It’ll be interesting to see if it’s ethical and safe and whether consolidation or reconsolidation is the preferred action
method.
The augmentation of exposure therapy has yet to be tested where it may be most helpful: as a treatment for incomplete responders to earlier SSRI or CBT. More basic research is needed to assess the universality of these drugs’ impact on non-target memory functions and their long-term utility as boosting agents. Blocking or reconsolidating fear-related memories is riddled with philosophical, practical, and ethical difficulties. Finally, the research on alternative augmentation processes involving psychedelic compounds is limited, unlikely to get past challenges regulatory without significant changes, and difficult to explain given the medications’ frequently serious side effects.
CONCLUSION
Although the use of pharmacological interventions when dealing with anxiety, we have established that pharmacological use is used on the recommendation on different types of stress and the fact that it is not exclusively used in all cases. Having understood that there is a need for extensive studies on the interventions of anxiety, at this particular moment, the best recommendation includes a mixture of all interventions where necessary for the best results. On the application side, the most pressing problems are about the best parameters and sequencing for existing treatments and the factors that influence therapy response and nonresponse at the individual level. These problems persist, even for first-line treatments like SSRIs. Other developing fields of research, such as the study of therapeutic response as a function of genetic markers, may one day allow clinicians to recommend the best starting medicines for their patients based on their unique genetic profiles. To develop innovative treatments, fundamental issues such as safety, tolerability, specificity, mechanism of action, and ethics must be addressed. As the decade progresses, research on the usage of existing medicines and analysis on the development of new treatments would complement one another.
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