Anxiety / Panic Attack

Introduction

Fear is an automatic neurophysiological state of alarm characterized by a fight or flight response to a cognitive appraisal of present or imminent danger (real or perceived). Anxiety is linked to fear and manifests as a future-oriented mood state that consists of a complex cognitive, affective, physiological, and behavioral response system associated with preparation for the anticipated events or circumstances perceived as threatening. Pathological anxiety is triggered when there is an overestimation of perceived threat or an erroneous danger appraisal of a situation which leads to excessive and inappropriate responses.

Associated Anatomy

The brain circuits and regions associated with anxiety disorders are beginning to be understood with the development of functional and structural imaging. The brain amygdala appears key in modulating fear and anxiety. Patients with anxiety disorders often show heightened amygdala response to anxiety cues. The amygdala and other limbic system structures are connected to prefrontal cortex regions. Hyperresponsiveness of the amygdala may relate to reduced activation thresholds when responding to perceived social threat.Prefrontal-limbic activation abnormalities have been shown to reverse with clinical response to psychologic or pharmacologic interventions

Causes

The first consideration is the possibility that anxiety is due to a known or unrecognized medical condition. Substance-induced anxiety disorder (over-the-counter medications, herbal medications, substances of abuse) is a diagnosis that often is missed.

Genetic factors significantly influence risk for many anxiety disorders. Environmental factors such as early childhood trauma can also contribute to risk for later anxiety disorders. The debate whether gene or environment is primary in anxiety disorders has evolved to a better understanding of the important role of the interaction between genes and environment.Some individuals appear resilient to stress, while others are vulnerable to stress, which precipitates an anxiety disorder.

Most presenting anxiety disorders are functional psychiatric disorders. Psychological theories range from explaining anxiety as a displacement of an intrapsychic conflict (psychodynamic models) to conditioning (learned) paradigms (cognitive-behavioral models). Many of these theories capture portions of the disorder.

The psychodynamic theory has explained anxiety as a conflict between the id and ego. Aggressive and impulsive drives may be experienced as unacceptable resulting in repression. These repressed drives may break through repression, producing automatic anxiety. The treatment uses exploration with the goal of understanding the underlying conflict. Cognitive theory has explained anxiety as the tendency to overestimate the potential for danger. Patients with anxiety disorder tend to imagine the worst possible scenario and avoid situations they think are dangerous, such as crowds, heights, or social interaction.

Causes of anxiety panic disorders

Panic disorder appears to be a genetically inherited neurochemical dysfunction that may involve autonomic imbalance; decreased GABA-ergic tone; allelic polymorphism of the catechol-O-methyltransferase (COMT) gene; increased adenosine receptor function; increased cortisol; diminished benzodiazepine receptor function; and disturbances in serotonin,serotonin transporter (5-HTTLPR)and promoter (SLC6A4) genes,norepinephrine, dopamine, cholecystokinin, and interleukin-1-beta.Some theorize that panic disorder may represent a state of chronic hyperventilation and carbon dioxide receptor hypersensitivity.Some epileptic patients have panic as a manifestation of their seizures. Genetic studies suggest that the chromosomal regions 13q, 14q, 22q, 4q31-q34, and probably 9q31 may be associated with the heritability of panic disorder phenotype.

The cognitive theory regarding panic is that patients with panic disorder have a heightened sensitivity to internal autonomic cues (eg, tachycardia). Triggers of panic can include the following:

• Injury (eg, accidents, surgery)
• Illness
• Interpersonal conflict or loss
• Use of cannabis (can be associated with panic attacks, perhaps because of breath-holding)
• Use of stimulants, such as caffeine, decongestants, cocaine, and sympathomimetics (eg, amphetamine, MDMA [“ecstasy”])
• Certain settings, such as stores and public transportation (especially in patients with agoraphobia).
• The SSRI discontinuation syndrome can induce symptoms similar to those experienced by panic patients.

In experimental settings, symptoms can be elicited in people with panic disorder by hyperventilation, inhalation of carbon dioxide, caffeine consumption, or intravenous infusions of hypertonic sodium lactate or hypertonic saline,cholecystokinin, isoproterenol, flumazenil,or naltrexone.The carbon dioxide inhalation challenge is especially provocative of panic symptoms in smokers.

Causes of social anxiety disorder (social phobia)

Genetic factors seem to play a role in social phobia. Based on family and twin studies, the risk for social phobia appears to be moderately heritable.

Social phobia can be initiated by traumatic social experience (eg, embarrassment) or by social skills deficits that produce recurring negative experiences. A hypersensitivity to rejection, perhaps related to serotonergic or dopaminergic dysfunction, is present. Current thought is that social phobia appears to be an interaction between biological and genetic factors and environmental events.

A psychoanalyst would likely conceptualize social anxiety as a symptom of a deeper conflict-for instance, low self-esteem or unresolved conflicts with internal objects. A behaviorist would see phobia as a learned, conditioned response resulting from a past association with a situation with negative emotional valence at the time of association (eg, social situations are avoided because intense anxiety was originally experienced in that setting). Even if no danger is posed in most social encounters, an avoidance response has been linked to these situations. Treatment from this perspective aims to weaken and eventually separate the specific response from the stimulus.

Causes of specific phobia

Genetic factors seem to play a role in specific phobia as well (eg, in blood-injury phobia), and the risk for such phobias also seems to be moderately heritable.In addition, specific phobia can be acquired by conditioning, modeling, or traumatic experience.

Causes of agoraphobia

Agoraphobia may be the result of repeat, unexpected panic attacks, which, in turn, may be linked to cognitive distortions, conditioned responses, and/or abnormalities in noradrenergic, serotonergic, or GABA-related neurotransmission.

Differential Diagnosis

Prior to medication treatment, testing for drugs of abuse, pregnancy, and screening tests for diabetes mellitus should be performed.

Anxiety disorders have one of the longest differential diagnosis lists of all psychiatric disorders. Anxiety is a nonspecific syndrome and can be due to a variety of medical or psychiatric syndromes. For example, a 2018 study found that about 30% of those with anxiety also have autoimmune thyroiditis (AIT).Additionally, a variety of anxiety symptoms, such as panic, worry, rumination, and obsessions, can present in a variety of psychiatric illnesses, including mood disorders, psychotic disorders, personality disorders, somatoform disorders, and cognitive impairment disorders (eg, delirium). Anxiety also can be observed as part of a drug withdrawal or drug intoxication effect.

Other important causes in the differential include medication-induced anxiety (ie, due to epinephrine or other sympathomimetics, theophylline or other neurostimulant bronchodilators, analgesics containing caffeine, corticosteroids, antivirals, others); migraine, seizure disorders, or other CNS-based disorders; and sleep disorders such as restless legs syndrome, sleep apnea, and periodic limb movement. Heroin abuse also should be considered in the differentials.

Clinicians should include following disorders and causes in differential diagnosis of anxiety:

• Acute Gastritis
• Acute Respiratory Distress Syndrome
• Addison Disease
• Adrenal Crisis
• Alcohol-Related Psychosis
• Alcoholism
• Amphetamine-Related Psychiatric Disorders
• Anaphylaxis
• Androgen Excess
• Anorexia Nervosa
• Asthma
• Atrial Fibrillation
• Atrial Tachycardia
• Body Dysmorphic Disorder
• Brief Psychotic Disorder
• Bulimia Nervosa
• Caffeine-Related Psychiatric Disorders
• Cannabis-Related Disorders
• Cardiogenic Shock
• Chronic Gastritis
• Conversion Disorders
• Delayed Hypersensitivity Reactions
• Delirium
• Delirium Tremens (DTs)
• Delusional Disorder
• Depression
• Diabetic Ketoacidosis (DKA)
• Diffuse Toxic Goiter (Graves Disease)
• Digitalis Toxicity
• Dissociative Disorders
• Dysthymic Disorder
• Encephalopathy, Dialysis
• Epilepsy Surgery
• Esophageal Motility Disorders
• Esophageal Spasm
• Euthyroid Hyperthyroxinemia
• Factitious Disorder Imposed on Self (Munchausen’s Syndrome)
• Folic Acid Deficiency
• Food Poisoning
• Geriatric Sleep Disorder
• Goiter
• Hallucinogen Use
• Hepatic Encephalopathy
• Hypercalcemia
• Hyperparathyroidism
• Hyperprolactinemia
• Hypertensive Encephalopathy
• Immediate Hypersensitivity Reactions
• Inhalant-Related Psychiatric Disorders
• Injecting Drug Use
• Insomnia
• Irritable Bowel Syndrome
• Lyme Disease
• Malingering
• Meningitis
• Multifocal Atrial Tachycardia
• Obstructive Sleep Apnea (OSA)
• Personality Disorders
• Phobic Disorders
• Premenstrual Dysphoric Disorder
• Primary Aldosteronism
• Primary Hypersomnia
• Primary Insomnia
• Rehabilitation and Fibromyalgia
• Schizoaffective Disorder
• Schizophrenia
• Shared Psychotic Disorder
• Sleep-Wake Disorders
• Somatic Symptom Disorders
• Stimulants
• Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
• Thyroiditis, Subacute
• Tourette Syndrome
• Type 1 Diabetes Mellitus
• Undifferentiated Connective-Tissue Disease
• Unstable Angina
• Uremic Encephalopathy

Drugs

Antidepressant agents are the drugs of choice in the treatment of anxiety disorders, particularly the newer agents that have a safer adverse effect profile and higher ease of use than the older tricyclic antidepressants (TCAs), such as selective serotonin reuptake inhibitors (SSRIs). Antidepressants that are not FDA-approved for the treatment of a given anxiety disorder, such as nefazodone and mirtazapine still may be beneficial. Older antidepressants, such as TCAs and monoamine oxidase inhibitors (MAOIs), also are effective in the treatment of some anxiety disorders.

A Cochrane review of second-generation antipsychotic drugs found that quetiapine and risperidone were effective when combined with antidepressants; however, adverse side effects were also reported.

Paroxetine (Paxil)

Alternative sedating SSRI. Potent selective inhibitor of neuronal serotonin reuptake. Also has weak effect on norepinephrine and dopamine neuronal reuptake. For maintenance dosing, make dosage adjustments to maintain patient on lowest effective dosage, and periodically reassess patient to determine need for continued treatment.

Escitalopram (Lexapro)

FDA approved for generalized anxiety disorder. SSRI and S-enantiomer of citalopram. Used for the treatment of depression. Mechanism of action is thought to be potentiation of serotonergic activity in central nervous system resulting from inhibition of CNS neuronal reuptake of serotonin. Onset of depression relief may be obtained after 1-2 wk, which is sooner than other antidepressants.

Sertraline (Zoloft)

FDA-approved for panic disorder, PTSD, social phobia, and OCD. May be helpful for other anxiety disorders.

Fluoxetine (Prozac)

FDA-approved for OCD and panic disorder. May be helpful for other anxiety disorders.

Fluvoxamine (Luvox)

FDA approved for OCD in children (8-17 y) and adults. May be helpful for other anxiety disorders.

Citalopram (Celexa)

Enhances serotonin activity due to selective reuptake inhibition at the neuronal membrane. Citalopram is a 50:50 racemate of r- and s-citalopram. Reports of dose-dependent QT interval limit dose escalation and coadministration with CYP2C19 inhibitors.

Venlafaxine (Effexor XR)

FDA-approved for generalized anxiety disorder, panic disorder and social anxiety disorder in adults. May be helpful for other anxiety disorders.

Duloxetine (Cymbalta)

Potent inhibitor of neuronal serotonin and norepinephrine reuptake. Indicated for generalized anxiety disorder.

Nefazodone (Serzone)

Antagonist at the 5-HT2 receptor and inhibits the reuptake of 5-HT. Also has negligible affinity for cholinergic and histaminergic receptors. Withdrawn from the US due to liver impairment.

Trazodone (Desyrel)

Useful in the treatment of panic disorders. Antagonist at the 5-HT2 receptor and inhibits the reuptake of 5-HT. Also has negligible affinity for cholinergic and histaminergic receptors.

In animals, selectively inhibits serotonin uptake by brain synaptosomes and potentiates the behavioral changes induced by the serotonin precursor 5-HTP.

Mirtazapine (Remeron)

Increases availability of serotonin and norepinephrine.

Imipramine (Tofranil)

Tricyclic antidepressant that has norepinephrine and serotonin reuptake-inhibition properties. One of the oldest agents available for the treatment of depression and has established efficacy in the treatment of panic disorder. Elderly and adolescent patients may need lower dosing or slower titration.

Amitriptyline (Elavil)

One of the oldest tricyclic antidepressant.

Desipramine (Norpramin)

Tricyclic antidepressant that has norepinephrine and serotonin reuptake-inhibition properties. One of the oldest agents available for the treatment of depression and has established efficacy in the treatment of panic disorder. Elderly and adolescent patients may need lower dosing or slower titration.

Clomipramine (Anafranil)

Dibenzazepine compound belonging to family of tricyclic antidepressants. Inhibits membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Clomipramine affects serotonin uptake while it affects norepinephrine uptake when converted into its metabolite desmethylclomipramine. Believed that these actions are responsible for its antidepressant activity.

Nortriptyline (Pamelor)

Has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the central nervous system. Pharmacodynamic effects such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play a role in its mechanisms of action.

Protriptyline (Vivactil)

Increases synaptic concentration of serotonin and/or norepinephrine in CNS by inhibiting their reuptake by the presynaptic neuronal membrane.

Doxepin (Sinequan)

Increases concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by presynaptic neuronal membrane. These effects are associated with a decrease in symptoms of depression.

Amoxapine

Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron. Metabolite (7-hydroxyamoxapine) has significant dopamine receptor blocking activity similar to haloperidol. Elicits strong anticholinergic effects.

Trimipramine (Surmontil)

Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron. Elicits strong anticholinergic effects.

Alprazolam (Xanax)

For management of anxiety attacks. Binds receptors at several sites within the central nervous system, including the limbic system and reticular formation. Effects may be mediated through GABA receptor system.

Lorazepam (Ativan)

Sedative hypnotic in the benzodiazepine class that has a short onset of effect and a relatively long half-life. By increasing action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, may depress all levels of the CNS, including limbic and reticular formation. Available for PO, IV, or IM use.

Clonazepam (Klonopin)

Long-acting benzodiazepine that increases the presynaptic GABA inhibition and reduces the monosynaptic and polysynaptic reflexes. Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters. Has multiple indications, including suppression of myoclonic, akinetic, or petit mal seizure activity and focal or generalized dystonias (eg, tardive dystonia). Reaches peak plasma concentration at 2-4 h after oral or rectal administration.

Diazepam (Valium)

Modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. Appears to act on part of the limbic system, the thalamus, and hypothalamus, to induce a calming effect. Also has been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.

Rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, serum concentration drops to 20% of Cmax.

Individualize dosage and increase cautiously to avoid adverse effects.

Chlordiazepoxide (Librium)

Depresses all levels of CNS, including limbic and reticular formation, possibly by increasing gamma-aminobutyric acid (GABA) activity, a major inhibitory neurotransmitter. Provides rapid onset and efficacy in sedating aggressive patients.

Oxazepam (Serax)

Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.

Buspirone (BuSpar)

5-HT1A agonist affecting serotonergic neurotransmission in CNS. Has some dopaminergic activity as well. In addition, has demonstrated anxiolytic effect but can take up to 2-3 wk for full efficacy. Also has a low abuse potential and does not mitigate panic attacks. Not useful in benzodiazepine withdrawal but has a low adverse-effect profile.

Risperidone (Risperdal)

Binds to dopamine D2 receptor with a 20-times lower affinity than for the 5-HT2 receptor. Improves negative symptoms of psychoses and reduces incidence of extrapyramidal adverse effects.

Response to antipsychotics is less dramatic than in true psychotic Axis I disorders, but symptoms such as anxiety, hostility, and sensitivity to rejection may be reduced. Antipsychotics are typically used for a short time while the symptoms are active.

Aripiprazole (Abilify)

Improves positive and negative schizophrenic symptoms. The mechanism of action is unknown but is hypothesized to work differently than other antipsychotics. Aripiprazole is thought to be a partial dopamine (D2) and serotonin (5HT1A) agonist and antagonize serotonin (5HT2A). Additionally, no QTc interval prolongation was noted in clinical trials. Available as tab, orally disintegrating tab, or oral solution.

Quetiapine (Seroquel)

May act by antagonizing dopamine and serotonin effects.

Newer antipsychotic used for long-term management. Improvements over earlier antipsychotics include fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia. Immediate- and extended-release formulations available.

Olanzapine (Zyprexa)

May inhibit serotonin, muscarinic, and dopamine effects. Response to antipsychotics is less dramatic than in true psychotic Axis I disorders, but symptoms such as anxiety, hostility, and sensitivity to rejection may be reduced. Antipsychotics are typically used for a short time while the symptoms are active.

Epidemiology

Anxiety is one of the most common psychiatric disorders in the general population. Specific phobia is the most common with a 12-month prevalence rate of 12.1%. Social anxiety disorder is the next most common, with a 12-month prevalence rate of 7.4%. The least common anxiety disorder is agoraphobia with a 12-month prevalence rate of 2.5%. Anxiety disorders occur more frequently in females than in males with an approximate 2:1 ratio.

The ECA study found no difference in rates of panic disorder among white, African American, or Hispanic populations in the United States.

Most anxiety disorders begin in childhood, adolescence, and early adulthood (see the image below). Separation anxiety is an anxiety disorder that commonly begins in childhood and often includes anxiety related to going to school. This disorder may be a precursor for adult anxiety disorders, most commonly panic disorder. According to the DSM-5, separation anxiety disorder can begin in adulthood.

Panic disorder demonstrates a bimodal age of onset in the NCS study in the age groups of 15-24 years and 45-54 years. The age of onset for OCD appears to be in the mid 20s to early 30s.

Most social phobias begin before age 20 years (median age at illness onset, 16 years).

Agoraphobia usually begins in late adolescence to early adulthood (median age at illness onset, 29 years).

In general, specific phobia appears earlier than social phobia or agoraphobia. The age of onset depends on the particular phobia. For example, animal phobia is most common at the elementary school level and appears at a mean age of 7 years; blood phobia appears at a mean age of 9 years; dental phobia appears at a mean age of 12 years; and claustrophobia appears at a mean age of 20 years. Most simple (specific) phobias develop during childhood (median age at illness onset, 15 years), and eventually disappear. Those that persist into adulthood rarely go away without treatment.

New-onset anxiety symptoms in older adults should prompt a search for an unrecognized general medical condition, a substance abuse disorder, or major depression with secondary anxiety symptoms.

Prognosis

Anxiety disorders have high rates of comorbidity with major depression and alcohol and drug abuse. Some of the increased morbidity and mortality associated with anxiety disorders may be related to this high rate of comorbidity. Anxiety disorders may contribute to morbidity and mortality through neuroendocrine and neuroimmune mechanisms or by direct neural stimulation, (eg, hypertension or cardiac arrhythmia). Chronic anxiety may be associated with increased risk for cardiovascular morbidity and mortality.

Considerable evidence shows that social phobia (social anxiety disorder) results in significant functional impairment and decreased quality of life.

Severe anxiety disorders may be complicated by suicide, with or without secondary mood disorders (eg, depression). The Epidemiological Catchment Area study found that panic disorder was associated with suicide attempts. How much of the association of panic disorder with suicide is mediated through the association of panic disorder with mood and substance abuse disorders is unclear. Acute stress may play a role in producing suicidal behavior. The presence of any anxiety disorder, phobias included, in combination with a mood disorder appears to increase likelihood of suicide attempts compared with a mood disorder alone.Suicide attempts can be precipitated by adverse life events such as divorce or financial disaster. The effects of acute stress in producing suicidal behavior are increased in those with underlying mood, anxiety, and substance abuse problems.

Phobias are highly comorbid. Most comorbid simple (specific) and social phobias are temporally primary, while most comorbid agoraphobia is temporally secondary. Comorbid phobias are generally more severe than pure phobias. Social phobia is also frequently comorbid with major depressive disorder and atypical depression, which results in increased disability.Despite evidence of impairment, only a minority of individuals with simple (specific) phobia ever seek professional treatment.

Interestingly, in clinical samples, over 95% of the patients reporting agoraphobia also present with panic disorder, while in epidemiologic samples, simple agoraphobia appears to be more prevalent than panic disorder with agoraphobia.

Natural Progression

Although there is no cure for anxiety disorder, it can be controlled with the right treatment. It is a chronic condition that can take many forms. The long-term outlook depends on the severity of the condition. Most people with OCD, phobias, and panic disorder improve greatly within the first weeks or months of proper treatment. Many people with PTSD and GAD can also make substantial improvement. Some symptoms of anxiety disorder may diminish with age.

Pathophysiology

In the central nervous system (CNS), the major mediators of the symptoms of anxiety disorders appear to be norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA). Other neurotransmitters and peptides, such as corticotropin-releasing factor, may be involved. Peripherally, the autonomic nervous system, especially the sympathetic nervous system, mediates many of the symptoms.

Positron emission tomography (PET) scanning has demonstrated increased flow in the right parahippocampal region and reduced serotonin type 1A receptor binding in the anterior and posterior cingulate and raphe of patients with panic disorder.MRI has demonstrated smaller temporal lobe volume despite normal hippocampal volume in these patients.The CSF in studies in humans shows elevated levels of orexin, also known as hypocretin, which is thought to play an important role in the pathogenesis of panic in rat models.

Possible Complications

Having an anxiety disorder does more than make you worry. It can also lead to, or worsen, other mental and physical conditions, such as:

• Depression (which often occurs with an anxiety disorder) or other mental health disorders
• Substance misuse
• Trouble sleeping (insomnia)
• Digestive or bowel problems
• Headaches and chronic pain
• Social isolation
• Problems functioning at school or work
• Poor quality of life
• Suicide

Possible Treatment

Treatment usually consists of a combination of pharmacotherapy and/or psychotherapy.Antidepressant agents are the drugs of choice in the treatment of anxiety disorders, particularly the newer agents, which have a safer adverse effect profile and higher ease of use than the older tricyclic antidepressants (TCAs), such as selective serotonin reuptake inhibitors (SSRIs). Antidepressants that are not FDA-approved for the treatment of a given anxiety disorder, such as nefazodone and mirtazapine, still may be beneficial. Older antidepressants, such as TCAs and monoamine oxidase inhibitors (MAOIs), also are effective in the treatment of some anxiety disorders.

Behavioral therapy and CBT have demonstrated efficacy through controlled studies.Computerized CBT (FearFighter) has been recommended for panic and phobia by the National Institute for Health and Clinical Excellence guidelines (NICE).Psychodynamic therapy (or insight-oriented therapy) is rarely indicated as an exclusive treatment for phobias and is now mostly used for cases of phobic disorders that overlap personality disorders. Interpersonal psychotherapy (IPT) has also shown some efficacy. Eight trials examined the use of IPT for anxiety disorders and found large effects in comparison with control groups. There was no evidence suggesting that IPT is less effective than CBT for anxiety.

In 2019, the FDA approved a cranial electrotherapy stimulator (CES) for treatment of anxiety, depression, and insomnia. The prescription device delivers micro pulses of electrical current across the brain, which in clinical trials led to a reduction in anxiety levels, insomnia, and depressed mood.It is the first CES integrated into noise-cancelling, Bluetooth-enabled headphones and the first CES managed through an app.

Deciding which treatment or combination of treatments to prescribe depends on a careful interview and assessment of the patient’s goals and level of pathology. The outcome of treatment is determined by several factors, including the following:

• Specific type of anxiety disorder
• Severity of diagnosis
• level of functioning prior to onset of symptoms
• Degree of motivation for treatment
• Level of support (eg, family, friends, work, school)
• Ability to comply with medication and/or psychotherapeutic regimen

Acute anxiety treatment

Patients with significant discomfort from their anxiety can benefit from emergency anxiolytic treatment, primarily with a benzodiazepine. In addition to ED treatment, patients in an acute anxious state of such severity that they pose a danger to themselves or to others should have a psychiatric consultation.

In the best of circumstances, a calm environment and social support from family, friends, and the emergency staff are ideal. For patients with more severe anxiety, a short course of a fast-acting anxiolytic agent is recommended. Chronic anxiety requires a comprehensive approach; the best pharmacotherapy varies for each individual, and outpatient follow-up with a psychiatrist is recommended. However, these patients can be discharged on a short course of benzodiazepines until they see a psychiatrist. Patients who express suicidal or homicidal thoughts should have an emergent psychiatric evaluation in the ED.

Generalized anxiety disorder treatment

Successful treatment approaches generally involve medication combined with psychotherapy. However, cognitive-behavioral therapy (CBT) has been proven superior in placebo-controlled trials. CBT generally includes self-reward as well as problem solving and can be as effective as medications, especially for children with mild generalized anxiety disorder.

Combining CBT with medications is extremely helpful in resistant cases.Other psychotherapies, such as relaxation therapy, supportive psychotherapy, or mindfulness therapy, have been used if CBT is not appropriate.

Indications for hospitalization include the following

• Severe functional impairment (cannot meet own daily needs)
• Suicide or homicide risk
• Social skills deficits (eg, the person is so preoccupied that he or she is unaware that his or her actions and behaviors have the potential to provoke others to cause harm)

Emotional intelligence is a protective factor for suicidal behavior; thus, this should be assessed as part of the decision regarding need for a psychiatric hospitalization.

Panic disorder treatment

Pharmacotherapy, cognitive and behavioral psychotherapy, and other psychological treatment modalities are all used to treat panic disorder. The 2011 American Psychiatric Association practice guideline for the treatment of patients with panic disorder strongly recommends SSRIs, other pharmacotherapy, or CBT as initial treatment. According to the guideline, there is insufficient evidence to recommend any of these pharmacological or psychosocial approaches as superior to the others, or to routinely prescribe a combination of treatments over monotherapy. Patient preference, and the availability of pharmacotherapy and specialized psychosocial treatments should be taken into consideration when choosing initial therapy for panic disorder.

Reassure and calm the patient. Untreated panic attacks can subside spontaneously within 20–30 minutes, especially with reassurance and a calming environment. Transport the patient to a medical treatment facility to exclude medical causes for the first attack or when suspected on subsequent attacks. The 2011 APA guidelines support this recommendation.

Primary Prevention

There’s no way to predict for certain what will cause someone to develop an anxiety disorder, but you can take steps to reduce the impact of symptoms if you’re anxious:

• Get help early. Anxiety, like many other mental health conditions, can be harder to treat if you wait.
• Stay active. Participate in activities that you enjoy and that make you feel good about yourself. Enjoy social interaction and caring relationships, which can lessen your worries.
• Avoid alcohol or drug use. Alcohol and drug use can cause or worsen anxiety. If you’re addicted to any of these substances, quitting can make you anxious. If you can’t quit on your own, see your doctor or find a support group to help you.

Secondary Prevention

There is no established method for the secondary prevention of anxiety. However medication adherence, joining an anxiety support group in the community and getting help on time from a mental health provider to figure out the triggers and address them is recommendable.

Risk factors

Close interaction between genetic and environmental factors is attributed for increased risk of anxiety:

• Depression
• Low socioeconomic status
• Alcohol
• Bipolar disorder
• Urbanization
• Stress
• Family history of anxiety
• Unemployment
• Substance abuse

Sign or Symptom

Generalized anxiety disorders:

• Excessive worry about multiple life events for a period of at least six months. The worry is disproportionate compared to the actual stressor
• Restlessness
• Fatigue
• Irritability
• Sleep disturbances
• Muscle tension
• Difficulty concentrating

Separation anxiety disorder:

• More common in children
• Recurrent excessive worry when anticipating or experiencing separation from home or major attachment figures
• Persistent worry about losing major attachment figures or about possible harm to them
• Repeated nightmares involving theme of separation
• Physical symptoms such as headaches, abdominal pain and other GI symptoms such as nausea and vomiting when separation from major attachment figures is anticipated.
• The disturbance has major limitation on functioning in social, occupational or academic setting
• The disturbance is not explained by any other mental disorder

Panic disorder:

• Palpitations
• Sweating
• Shaking
• Chest pain
• Shortness of breath
• Dizziness
• Paresthesias
• Fear of going crazy
• Depersonalization
• Fear of dying
• The disturbance is not attributed to any other mental disorder
• The disorder is not due to physiologic effect of a substance
• The disturbance has major limitation on functioning in social, occupational or academic setting

Social anxiety disorder:

• Excessive anxiety about social situations where the individual is worried about scrutiny by others
• Excessive anxiety in social situations such as having a conversation, parties, performing in front of a crowd(e.g.,Public speaking)
• Avoidance of social situations
• The anxiety significantly impairs functioning in all aspects of life
• The anxiety is not due to any other mental, medical or substance abuse

Agoraphobia:

• Fear of places or circumstances , where an individual perceives as difficult to escape
• Marked fear of the following situations:
• Being in open spaces
• Being outside alone
• Being in closed spaces(e.g., Cinemas, shops), which the individual perceives escape is difficult in case of an emergency
• Being in crowded places (e.g., public transportation, buses, trains)
• The disorder causes significant disturbance in important areas of functioning
• The disorder is not explained by any other mental disorder

Substance/medication induced anxiety disorder:

• Symptoms of worry beginning during or aftersubstance intoxication or after taking a medication
• There is evidence from the history, physical examination ,or laboratory findings of symptoms like anxiety and panic attack developed during or soon after substance intoxication or withdrawal or exposure to a medication
• The disorder is not due to delirium
• The disorder causes significant functional impairment

Selective mutism

• Failure to speak in certain situations in which there is an expectation for speaking(e.g., school) but is able to speak at home
• The failure to speak is not due to lack of knowledge or language impairment
• The duration lasts at least a month
• The disorder does not occur during the course of autism spectrum disorder , schizophrenia or any other psychotic disorder

Specific phobia

• Persistent fear of a certain object or situation(e.g., fear of heights, fear of animals)
• The fear or avoidance behavior lasts at least for six months
• The fear is out of proportion to the actual stressor
• The fear causes significant functional impairment

Anxiety due to another medical condition

• Fear is due to direct result of a medical condition
• Anxiety and panic attacks
• The disorder does not occur during the course of a delirium
• The disorder not attributed to any other mental disorder
• The disorder causes significant functional impairment

Unspecified anxiety disorder

This classification applies to conditions in which anxiety is predominant but do not meet full criteria for any of the disorders in the DSM-5 classification of anxiety disorders

Stage

There are different levels of anxiety:

Mild anxiety

Generally speaking, mild anxiety is the type that most of us experience on a day-to-day basis during certain situations. Patient may have an uneasy feeling in your stomach, and may feel pulse increase slightly. But anxiety at this level can also be beneficial, as it can help us to focus and increases your alertness.

Moderate anxiety

Moderate anxiety is similar to mild anxiety but can become more severe and overwhelming, making us feel more nervous and agitated.

Moderate anxiety can mean patients place their complete attention on the thing or situation that’s making feel anxious and ignore everything else around them. They may start to experience stronger physical and emotional anxiety symptoms such as muscle tension, sweaty palms, a shaky voice, back pain and changes in their sleep pattern. Emotionally they may feel more sensitive and excited than normal, and they may also feel less confident.

Severe anxiety

Severe anxiety is the highest level, when the patient stop being able to think rationally and experience severe panic. The patient may feel afraid and confused, agitated, withdrawn and may also find it difficult to think clearly. Breathing may quicken and the patient may start to perspire while his/her muscles will become very tense.

Studies

Active Not Recruiting

Number of studies: 142

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Completed

Number of studies: 1, 817

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Enrolling by Invitation

Number of studies: 45

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Not Yet Recruiting

Number of studies: 196

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Recruiting

Number of studies: 645

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Results Available

Number of studies: 344

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Results Not available

Number of studies: 3, 029

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Suspended

Number of studies: 7

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Terminated

Number of studies: 133

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Withdrawn

Number of studies: 66

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Sub Type

Several types of anxiety disorders exist:

• Agoraphobia is a type of anxiety disorder in patient fear and often avoid places or situations that might cause him/her to panic and make you feel trapped, helpless or embarrassed.
• Anxiety disorder due to a medical condition includes symptoms of intense anxiety or panic that are directly caused by a physical health problem.
• Generalized anxiety disorder includes persistent and excessive anxiety and worry about activities or events — even ordinary, routine issues. The worry is out of proportion to the actual circumstance, is difficult to control and affects how you feel physically. It often occurs along with other anxiety disorders or depression.
• Panic disorder involves repeated episodes of sudden feelings of intense anxiety and fear or terror that reach a peak within minutes (panic attacks). Patients may have feelings of impending doom, shortness of breath, chest pain, or a rapid, fluttering or pounding heart (heart palpitations). These panic attacks may lead to worrying about them happening again or avoiding situations in which they’ve occurred.
• Selective mutism is a consistent failure of children to speak in certain situations, such as school, even when they can speak in other situations, such as at home with close family members. This can interfere with school, work and social functioning.
• Separation anxiety disorder is a childhood disorder characterized by anxiety that’s excessive for the child’s developmental level and related to separation from parents or others who have parental roles.
• Social anxiety disorder (social phobia) involves high levels of anxiety, fear and avoidance of social situations due to feelings of embarrassment, self-consciousness and concern about being judged or viewed negatively by others.
• Specific phobias are characterized by major anxiety when you’re exposed to a specific object or situation and a desire to avoid it. Phobias provoke panic attacks in some people.
• Substance-induced anxiety disorder is characterized by symptoms of intense anxiety or panic that are a direct result of misusing drugs, taking medications, being exposed to a toxic substance or withdrawal from drugs.
• Other specified anxiety disorder and unspecified anxiety disorder are terms for anxiety or phobias that don’t meet the exact criteria for any other anxiety disorders but are significant enough to be distressing and disruptive.

Typical Test

Mental Status Examination

A complete mental status examination should be obtained for each patient with anxiety symptoms, assessing appearance, behavior, ability to cooperate with the exam, level of activity, speech, mood and affect, thought processes and content, insight, and judgment. Patients may exhibit physical signs of anxiety such as sweaty palms, restlessness, and distractibility. Patients are generally oriented times 3 and cooperative. Mood may be normal or depressed. Affect is often preserved. Psychotic symptoms are not typical of uncomplicated anxiety disorders. Suicidal ideation should be assessed by asking about passive thoughts of death, desires to be dead, thoughts of harming self, or plans or acts to harm self. Homicidal ideation is uncommon. Cognition is typically intact with no impairment in memory, language, or speech. Insight and judgment are typically intact.

Physical Examination

Because anxiety manifests with a number of physical symptoms, any patient who presents with a de novo complaint of physical symptoms suggesting an anxiety disorder should have a physical examination and basic laboratory workup to rule out medical conditions that might present with anxiety like symptoms.

For a patient who presents for a repeat visit with similar complaints, after medical contributors have been ruled out, a careful mental status examination might be better suited than repeat physical examination and laboratory investigations. (See Mental Status Examination.) While considering anxiety as the primary suspect, the physician should always remember that over time patients with anxiety do develop medical conditions at the same rate as other patients. In other words, a diagnosis of anxiety, while changing the threshold for investigation of physical symptoms, should not deprive the patient of regular follow-up examinations as otherwise indicated.

Laboratory tests

The diagnosis of anxiety is mostly clinical, based on a thorough history and physical exam. There is a limited role for laboratory tests in the diagnosis of anxiety; however, they may be used for to rule out other medical causes that cause anxiety.

Electrocardiogram

The EKG in anxiety is characterized by sinus tachycardia.

MRI and PET

High resolution MRI and PET in anxiety shows increased volume of amygdala.

Studies to exclude anxiety

For presentations with a higher index of suspicion for other medical causes of anxiety (ie, atypical anxiety disorder presentation, older age, specific physical examination abnormalities), more detailed evaluations may be indicated to identify or exclude underlying medical disorders.

Electroencephalography, lumbar puncture, and head/brain imaging

Rule out CNS disorder using electroencephalography (EEG), lumbar puncture, or brain computed tomography (CT) scan, as indicated by history and associated clinical findings. EEG may be used to exclude seizure disorder because these conditions may mimic anxiety.

Imaging studies are limited to presentations in which medical illness, such as a seizure disorder, is suspected. If headache is a prominent feature, an EEG or MRI could be considered along with neurologic consultation to rule out seizures or brain tumor. A head CT scan may be ordered for suspected intracranial abnormality, or an MRI scan for intracranial abnormality.

Functional MRI and PET scanning have shown increases in blood flow and metabolic activity in the orbitofrontal cortex, limbic structures, caudate, and thalamus, with a trend toward right-sided predominance, in patients with obsessive-compulsive disorder. In some studies, these areas of overactivity have been shown to normalize following successful treatment with either SSRIs or CBT. [41] These imaging modalities, however, are of value for research, and not indicated for normal workups.

Electrocardiography

Rule out cardiac disorders (eg, myocardial infarction) using electrocardiography (ECG) or treadmill ECG. ECG may be used to check for mitral valve prolapse or to exclude arrhythmia.

Tests for infection

Rule out infectious causes using rapid plasma reagent test, lumbar puncture (CNS infections), or HIV testing.

Arterial blood gas analysis

Arterial blood gas analysis is useful in confirming hyperventilation (respiratory alkalosis) and excluding hypoxemia or metabolic acidosis. The presence of hypoxemia with hypocapnia or a widened alveolar-arterial (A-a) gradient should increase the suspicion of pulmonary embolus.

Electrolyte analysis

Electrolyte analysis is unnecessary, although several abnormalities may be present in the setting of hyperventilation. Serum phosphorus and ionized calcium may be diminished in patients with hyperventilation and carpopedal spasm, Chvostek sign, or Trousseau sign. The serum calcium level may be within the reference range.

Chest radiography

Chest radiography is useful in excluding other causes of dyspnea with chest pain (eg, pulmonary embolism).

Thyroid function

Hyperthyroidism is one of the most common medical causes for anxiety related to a medical condition. Serum thyroid-stimulating hormone and T4 levels should be considered for excluding a primary thyroid abnormality.

 

Reference

https://emedicine.medscape.com/article/286227-overview#showall
https://medlineplus.gov/anxiety.html
https://www.mayoclinic.org/diseases-conditions/anxiety/symptoms-causes/syc-20350961
https://www.uptodate.com/contents/panic-disorder-in-adults-epidemiology-pathogenesis-clinical-manifestations-course-assessment-and-diagnosis
https://www.wikidoc.org/index.php/Anxiety
https://clinicaltrials.gov