Approach Considerations
Treatment usually consists of a combination of pharmacotherapy (see Medication) and/or psychotherapy. [42] 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. [43] Computerized CBT (FearFighter) has been recommended for panic and phobia by the National Institute for Health and Clinical Excellence guidelines (NICE). [44] 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. [45]
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. [46] It is the first CES integrated into noise-cancelling, Bluetooth-enabled headphones and the first CES managed through an app. [47]
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:
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Specific type of anxiety disorder
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Severity of diagnosis
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level of functioning prior to onset of symptoms
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Degree of motivation for treatment
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Level of support (eg, family, friends, work, school)
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Ability to comply with medication and/or psychotherapeutic regimen
Acute anxiety
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
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. [48]
Combining CBT with medications is extremely helpful in resistant cases. [49, 50] Other psychotherapies, such as relaxation therapy, supportive psychotherapy, or mindfulness therapy, have been used if CBT is not appropriate. [51]
Indications for hospitalization include the following
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Severe functional impairment (cannot meet own daily needs)
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Suicide or homicide risk
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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. [38]
Panic disorder
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. [52]
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. [52]
Pharmacotherapy for Anxiety and Panic Disorders
Selective serotonin reuptake inhibitors (SSRIs) are generally used as first-line agents, followed remotely by tricyclic antidepressants (TCAs).
Fluoxetine (Prozac) can be used (especially if panic disorder occurs with depression); however, patients may poorly tolerate it initially because it may initially increase anxiety, except at very low starting doses. Fluoxetine has a long half-life, making it a good choice in marginally compliant patients. It alters metabolism of cytochrome P-450 2D6-cleared agents; this fact should be considered.
Paroxetine (Paxil) represents a partially sedating SSRI option that is also available in a controlled-release preparation (Paxil CR), which may improve tolerability, but paroxetine still inhibits P450 2D6. Paroxetine has a short half-life, which may be a limitation in marginally compliant patients.
Citalopram (Celexa) carries a risk of dose-dependent QT prolongation. Because of the risk for QT prolongation, citalopram is contraindicated in individuals with congenital long QT syndrome and the dose should not exceed 40 mg/day. Do not exceed a dose of 20 mg/day when coadministered with CYP2C19 inhibitors (eg, cimetidine, fluconazole, omeprazole). [53, 54]
Escitalopram (Lexapro) is likely to cause fewer hepatic enzyme interactions and may be appropriate initial choices for patients with complicated medical regimens or those who are concerned about drug interactions. Escitalopram also appears to be particularly well tolerated in preliminary studies, although it may be restricted from some formularies due to the large difference in cost with citalopram without a commensurate improvement in efficacy or tolerability for many patients.
Sertraline (Zoloft) represents a similar SSRI option with a slightly different pharmacodynamic profile, including sigma receptor effects, although it has some P450 3A4 interactions.
Mirtazapine (Remeron) [55] has a much more sedating effect, generally reducing its potential to aggravate initial anxiety. Mirtazapine acts distinctly as an alpha-2 antagonist, consequently increasing synaptic norepinephrine and serotonin, while also blocking some postsynaptic serotonergic receptors that conceptually mediate excessive anxiety when stimulated with serotonin.
Mirtazapine may cause residual morning sedation that often improves with continued therapy and may cause an increase in appetite or weight gain. A study by Kim et al suggests among patients with major depressive disorder who have high anxiety symptoms, mirtazapine (15-30 mg/d) administered in the early weeks of treatment may have an earlier-onset action for anxiety symptoms. [56]
Sedating antidepressants such as paroxetine, mirtazapine, and other TCAs/TeCAs are usually prescribed only at night before bed to help improve sleep but should include a warning not to operate a motor vehicle or machinery if feeling sedated or directly after the dose.
Initiation of antidepressant agents are thought to cause early worsening of anxiety, agitation, and irritability, particularly when used to treat anxiety. Sinclair et al use the term jitteriness/anxiety syndrome to describe these effects and completed a systematic search of articles that describe these effects. [57]
No validated rating scales for jitteriness/anxiety syndrome were identified among 107 articles included in the review. No evidence indicated a difference in incidence of jitteriness/anxiety syndrome between SSRIs and TCAs, and a higher incidence was not observed in anxiety disorders. Incidence rates of jitteriness/anxiety syndrome varied widely in the published literature (4–65%).
The authors concluded that jitteriness/anxiety syndrome is poorly characterized, but perception of this syndrome influences clinician prescribing. They recommend more evaluation of adverse effects at early points during antidepressant trials to more comprehensively describe this syndrome.
Intravenous or oral acute sedation with benzodiazepines may be used. Alprazolam (Xanax) has been widely used for panic disorder, but it is currently discouraged because of its higher dependence potential; alprazolam has a short half-life, which makes it particularly prone to rebound anxiety and psychological dependence. Clonazepam (Klonopin) has become a favored replacement because it has a longer half-life and empirically elicits fewer withdrawal reactions upon discontinuation.
Prompt use of benzodiazepines can ease the uncomfortable anxiety associated with the attack and can provide the patient with definitive confidence that treatment can control the symptoms. This is particularly helpful for preventing subsequent visits to emergency services while longer-term therapy is helping the patient gain control.
Benzodiazepines act quickly but carry the liability of physiologic and psychologic dependence. They can be reasonably used as an initial adjunct while SSRIs are titrated to an effective dose, and they can then be tapered over 4-12 weeks while the SSRI is continued. This approach can improve short-term tolerability, although it may increase the risk of sedation and requires warnings not to operate motor vehicles after taking benzodiazepines or if feeling sedated. If possible, avoid long-term benzodiazepines for chronic anxiety disorders. Benzodiazepines can achieve long-term control but should be reserved for patients with refractory panic disorder and should generate a psychiatric referral for pharmacologic management review and potentially a psychotherapist for any additional nonpharmacologic treatment options.
Psychotherapy for Anxiety and Panic Disorders
Cognitive and behavioral psychotherapy can be used alone or in addition to pharmacotherapy. The combination approach yields superior results for most patients compared to either single modality.
Cognitive therapy helps patients understand how automatic thoughts and false beliefs/distortions lead to exaggerated emotional responses, such as anxiety, and can lead to secondary behavioral consequences. Specific patterns of cognitive distortions (twisted thoughts) tend to respond best to specific techniques described in cognitive behavior therapy books (eg, The Feeling Good Handbook by David Burns, MD). While intended for use in conjunction with therapy, patients can purchase these books and complete the course themselves.
Behavioral therapy involves sequentially greater exposure of the patient to anxiety-provoking stimuli; over time, the patient becomes desensitized to the experience. Relaxation techniques also help control patients' levels of anxiety. Respiratory training can help control hyperventilation during panic attacks and help patients control anxiety with controlled breathing. Other forms of psychological treatment, including psychodynamic psychotherapy for specific issues, are available but exceed the scope of this article.
Consultation with a psychiatrist is helpful to initiate longer-term therapy and to provide follow-up planning. Longer-term therapy currently consists of SSRIs, often with additional psychotherapeutic techniques.
The 2011 APA guidelines state the importance of monitoring changes in key symptoms such as frequency and intensity of panic attacks after treatment has been started. Treatment is effective if it produces a decrease in panic symptoms, although some symptoms may respond more quickly than others. For those individuals who do not respond, or respond incompletely, to initial treatments for panic disorder, treatment modalities should be reassessed. [52]
Phobic Disorders
Social phobia (social anxiety disorder)
Both psychotherapy and pharmacotherapy are useful in treating social phobia. Self-exposure monotherapy is recommended for this phobia, as it has been shown to work as well as computerized-based exposure training, clinician-led exposure, or combinations therapies of self-exposure and CBT/self-help manual. [58]
A systematic review of self-help interventions for psychiatric disorders suggests this appears to be an effective way of treating individuals diagnosed with social phobia and panic disorder. The addition of clinician support and the presentation of multimedia or web-based self-help materials improved treatment outcome. Further research is needed to determine the cost-effectiveness and acceptability of these methods. [59]
Social phobia typically responds to either an SSRI or a monoamine oxidase inhibitor (MAOI). [60, 61, 62] Initiate treatment with an SSRI and titrate to the minimum effective dose. SSRIs approved for social phobia include paroxetine [63] (including SR form) and sertraline, but other SSRIs have also been shown to be effective (eg, fluvoxamine [64] ). The SSRI dose can be increased if response is partial or nonexistent at 6 weeks—doses can be increased every 2 weeks until maximum dose is reached.
Failing this, patients sometimes respond to high-potency benzodiazepines. Long-term treatment data from clinical studies of clonazepam are limited but support the drug’s efficacy. [65] Beta-blockers, clonidine, and buspirone are usually not helpful for long-term treatment, although a beta-blocker such as atenolol, nadolol, or propranolol may be useful for the circumscribed treatment of situational/performance anxiety on an as-needed basis.
Consider tapering medications slowly after 6-12 months of full response. If symptoms reoccur following taper, restart therapy and continue indefinitely. [65]
Specific (simple) phobia
Specific phobias respond well to CBT. Gradual desensitization is the most commonly used treatment. Randomized, controlled clinical trials indicate that specific (simple) phobias also respond to exposure therapy. [66] A small, randomized, controlled clinical trial showed that virtual reality exposure (VRE) therapy is as effective as standard exposure (SE) therapy for fear of flying, with gains maintained up to 1 year following the treatment. [67]
Other treatments include cognitive approaches, relaxation, and breathing control techniques. To date, no controlled studies demonstrate the efficacy of psychopharmacologic intervention for specific phobias.
Agoraphobia
Agoraphobia (specifically, the panic symptoms) most often responds to treatment with an SSRI. [68, 69, 70] Treatment should be started at a low dose then titrated to the minimum effective dose for controlling the patient’s panic. Benzodiazepines can be used either as an adjunct or as primary treatment; however, benzodiazepines are usually not chosen as a first-line treatment because of the potential for abuse. [71] If the patient has frequent panic attacks and no history of substance abuse, a benzodiazepine can be considered until the SSRI takes effect. Long-acting benzodiazepines (eg, diazepam, clonazepam) prescribed on a standing rather than on an as-needed basis are preferred due to a lower addictive potential; dose can be increased every 2-3 days until panic symptoms are controlled or the maximum dose is reached.
Consider using the short-acting alprazolam for short-term use to control acute symptoms of panic. If response is minimal or nonexistent after 6 weeks, the SSRI dose can be further increased every 2 weeks until response or maximal dose is reached. Partial or no response at the highest SSRI dose warrants consideration of the following alternatives: change to a different SSRI; change to a different class (venlafaxine, duloxetine); change to TCAs/TeCAs or MAOIs (both TCAs/TeCAs and MAOIs have demonstrated efficacy in controlled trials for agoraphobia).
For a patient with good response, treatment should be continued for 9-12 months before considering slowly tapering the medications. With symptom recurrence following taper, treatment should be resumed and continued indefinitely.
Diet
Caffeine-containing products, such as coffee, tea, and colas, should be discontinued (or decreased to a low reasonable level). Over-the-counter preparations and herbal remedies should be reviewed with special caution because ephedrine and other herbal compounds may precipitate or exacerbate anxiety symptoms. The use of some gentle herbal preparations may be considered in persons who do not have allergies or sensitivities to those agents. [72]
Consultations
Most often, psychiatrists are consulted. Psychology consultation and testing is indicated if cognitive impairment is of concern or if the patient may be a candidate for CBT. Social work consultation may be helpful if coping skills are markedly impaired.
In anxiety disorders secondary to a general medical condition, specialty consultation may be indicated. Cardiology consultation is indicated when symptoms include heart rate irregularity or abnormal blood pressure. Neurology consultation is indicated when symptoms include headaches or visual field abnormalities, balance abnormalities, or mental status changes. Endocrinology consultation is indicated when symptoms include heat or cold intolerance, problems with fluid balance, or mood swings due to cortisol abnormalities.
To reduce muscle tension, manual manipulation or massage therapy can be helpful in nonpharmacologic approaches. Treatment with a licensed practitioner is important, as there have been cases of sexual abuse or battery with nonlicensed nonprofessionals.
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Anxiety. Chart showing the female-to-male sex ratio for anxiety disorders. Adapted from Kessler et al, 1994.
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Anxiety. Age of onset for anxiety disorders based on specific anxiety disorder type.
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Brain structures involved in dealing with fear and stress.
