Anxiety is a universal, adaptive human experience keeping us alert and safe from danger. It produces our “fight or flight” responses to perceived threats. Anxiety is also a motivating emotion under normal circumstances, driving us to action to achieve goals. When anxiety reaches significant heights, however, it becomes problematic and creates multiple physical symptoms, maladaptive behaviors, and extraordinary human misery—in addition to psychological symptoms of worry or fear.
Anxiety problems may range from mild and annoying physical symptoms that cause little worry to disorders where patients’ lives are filled with dread, incapacitating physical symptoms, and avoidant behavior(s) that can reach paralyzing proportions. Anyone who has been acutely frightened or placed in unexpected stressful situations can easily identify the emotional and physical symptoms that accompany the experience of anxiety.
Anxiety disorders are the most common psychiatric illnesses overall.1 Although they may occur at any time in the life cycle, they usually have their onset during adolescence and young adulthood and can become a life-long burden.2 A recent comprehensive “review of the reviews” of the prevalence of anxiety disorders reveals wide ranges of prevalence, upwards of 25% for “any disorder.”3 The prevalence was particularly high in women, young adults, persons with chronic illnesses, and individuals from Anglo-European cultures.
The neurobiological basis of the anxiety disorders involves “loop networks” within the brain. The fundamental structures recognizing and responding to threat in the environment include the thalamus, amygdala, dorsal anterior cingulate cortex (dACC), hypothalamus, hippocampus, and medial prefrontal cortex (mPFC).4 The thalamus is the structure that integrates all sensory input, then sending it to the hypothalamus. The amygdala and dACC process threatening stimuli and send it to the hypothalamus which relays it to the basal ganglia and brainstem resulting in rapid, unconscious, and reflexively defensive behaviors such as startle responses and sudden muscular withdrawal. The contextual features of threat are encoded in memory by the hippocampus. The mPFC is then involved in the “top down” regulation of the threat information resulting in an adaptive, conscious response. Several investigative methods have identified specific neural loops producing nuanced differences that correlate with specific anxiety disorders.4 The major neurotransmitter pathways involved in anxiety are the GABA, noradrenergic, and serotonergic systems that provide the basis for pharmacologic treatment strategies.5
DIAGNOSTIC AND TREATMENT ISSUES COMMON TO ALL ANXIETY DISORDERS
The anxiety disorders in DSM-5 have many overlapping symptoms and features in common.6 They have, however, important distinguishing features critical to effective differential diagnosis. Likewise, anxiety treatments overlap with depression and among the various anxiety disorders themselves. This makes treatment easier because the doses and regimens are similar in the various disorders, although often starting lower and increasing more slowly with the anxiety disorders.
Primary care providers must also consider all the patients who struggle with symptoms of anxiety including those whose anxiety does not reach the DSM-5 threshold for a diagnosis. Patients with significant but “subthreshold” anxiety still suffer and their ongoing stress responses complicate all facets of their lives and especially underlying medical problems.
Anxiety is a leading cause of physical symptoms in primary care. To begin, most patients with anxiety disorders have prominent physical symptoms, as reviewed in Chapters 1 and 2. To complicate your diagnostic approach, however, there are many medical conditions associated with anxiety; see Table 5-1. In general, anxiety manifested by physical symptoms in younger people is most likely due to an anxiety disorder itself, while in patients over 50 years of age, it is more likely that anxiety symptoms complicate an underlying medical condition. For example, certain rare or uncommon medical conditions directly cause anxiety; for example, pheochromocytoma, carcinoid, and hyperthyroidism. More commonly, however, chronic medical conditions cause anxiety because of their debilitating and disabling effects. As well, prescribed and over-the-counter medication use and recreational substance use cause anxiety and are additional differential diagnostic considerations; see Table 5-2.
Physical symptoms commonly associated with anxiety disorders include shortness of breath, sleep disturbance (especially initial insomnia—taking more than 30 minutes to get to sleep), muscular tension, headache, restlessness, and gastrointestinal upset. For physical and psychological anxiety symptoms, an easy and helpful strategy to guide the diagnostic workup and intervention is the A-B-C Model.7
This initial strategy helps to engage patients in how they first became aware of and experienced their anxiety, how they cognitively interpreted it, and the actions they took to cope with it. The following is an example of some of the typical anxiety and physical symptoms of pretreatment panic disorder. The patient is a 21-year-old female college student.
ALARM: Initial feelings of uneasiness followed by anxiety and its escalation: “I’m getting really nervous; now my heart is pounding; my chest feels tight, I can’t catch my breath; I’m sweating; my lips are tingling. This has never happened to me before. Am I dying?”
BELIEF: “I’m having a heart attack.” Or, “I can’t control this, I must be going crazy.”
COPING: “Call 911, I have to get to an emergency room.”
Now we see the same patient in the initial phase of a successful intervention:
ALARM: “Here we go again, the emergency room doctor and my primary care doctor said this might happen again before my medication started to work fully.”
BELIEF: “I’m having another panic attack. This will be unpleasant but not dangerous to me.”
COPING: “I will sit down, start my mindfulness and breathing control exercises and manage this.”
This strategy also assists in structuring the history, planning an efficient and cost-effective diagnostic workup, and making the best differential diagnosis. Because the interrelationship between anxiety and physical symptoms can be multifactorial, a familiarity with the underlying medical conditions frequently associated with anxiety is important. Typically, workups need not lead to invasive tests and thereby risk iatrogenic complications, especially in young people. (See Table 5-1, where we suggest initial screening testing if the history and physical examination is inconclusive.) Further, summarized in Table 5-2, anxiety can be an adverse effect of commonly prescribed classes of medications, substances of abuse, and both over-the-counter medicines and nutritional supplements; for example, caffeine is a common cause as is excessive thyroid medication. Diligent history-taking in this component of the workup is critical. Treatment may be as simple as dosage adjustment, discontinuation, or switch to another indicated medication.
The Mental Health Care Model (MHCM) discussed in Chapter 3 provides guidance for diagnosing and managing anxiety disorders.
Patient-centered interactions are essential. The most important general treatment strategy for all anxiety disorders is establishing a trusting relationship with the primary care provider. Empathy (using NURS skills) is important because many patients with anxiety disorders have been subject to criticism, referred to in pejorative terms, and ridiculed by others. Empathic connection facilitates cooperation with and adherence to instructions made for general self-help measures like a healthy diet, exercise, relaxation techniques, and principles of sleep hygiene. Pharmacologic treatments often do not work immediately while a number of possible untoward/adverse effects may occur early on. The trusting relationship helps patients to have realistic expectations in the trajectory of their recovery and to persist with dosage increases/adjustments of their medications. The clinician-patient relationship is also essential when making a referral to a mental health professional (psychiatrist, psychologist, medical social worker, other counselors), especially if the patient indicates resistance to this suggestion. When making the mental health referral it is critical to reinforce that this will be just one component of their overall primary care. See Chapter 11 for referral principles.
Education: It is important to always ascertain the patient’s understanding of the problem in order to correct any misunderstandings (eg, selective serotonin reuptake inhibitors [SSRIs] don’t work for anxiety, benzodiazepines are the best treatment). Once assured that they have a clear and accurate understanding of the problem, you can indicate that very effective treatments exist and that you will prescribe the most appropriate one for them.
Commitment and goals: Always determine the degree of commitment a patient has, as well as their goals, particularly in describing treatment, looking for any resistances that you may need to address further. It is important to initially establish long-range goals (eg, getting back to work, feeling more comfortable socially), frequently revisiting them at later visits.
Treatment plan: The remainder of this chapter addresses general and specific treatments as they apply to the various anxiety disorders.
To review some features of the MHCM especially helpful in anxiety, mindfulness-based therapy is a self-help intervention that involves recognition of one’s emotional state followed by “in-the-moment” focused awareness. The mindful awareness achieved is a form of meditation that promotes relaxation and stress reduction. Mindfulness therapies are customized to each individual patient’s circumstances.8 While you are evaluating the patient’s progress with pharmacological treatment, be sure to also review clinical progress with self-help efforts. In Chapter 3, see Table 3-4 for a simple meditation procedure.
Patients experiencing significant anxiety require special attention to improvement in their general health, especially a healthy diet and their level of physical fitness. A graded physical exercise program that includes both aerobic and resistance training is effective in both reducing anxiety symptoms and improving overall physical fitness.9 Exercise programs must be carefully negotiated and tailored to each patient’s current health status. Learning to practice Yoga, either by joining a class or individually by following an introductory DVD, assists with neuromuscular anxiety relaxation and reducing anxiety states.10
Psychotherapy in all its forms and iterations decreases anxiety symptoms in most anxiety disorders. Although outside the scope of the clinician, it is important to have a sense of what occurs. Cognitive behavioral therapy (CBT) has been foremost and especially successful for long-term remission.11 (Insight-oriented psychotherapy is a more extensive and deeply reaching process.) Clinicians can refer their patients to mental health professionals trained in this technique. Although most psychiatrists now focus almost exclusively on pharmacological treatment, a psychologist and/or skilled social worker can conduct CBT (or other therapy) and become part of the treatment team. As the clinician, you remain involved with the patient’s overall care, often prescribing medications in parallel, as we outline later for each disorder. Patients generally find CBT very useful as they learn new coping strategies and experience symptom reduction. Avoidant behavior is a common consequence of all anxiety disorders and mental health professionals generally address it using exposure techniques. The general principle is “Confronting what makes you anxious makes it better, avoiding what makes you anxious makes it worse.” The usual technique is gradual reexposure. For your patients who refuse referral, encourage them to create their own independent trial of graded confrontation.
With this general backdrop of diagnosis and treatment of anxiety disorders, we now address the specific disorders, including pharmacotherapy for each. A recent meta-analysis indicates that both psychotherapy and medications for anxiety disorders are not only effective but also that they have enduring impact after treatment.12
GENERALIZED ANXIETY DISORDER
Generalized anxiety disorder (GAD) is a chronic illness characterized by waxing, especially in times of increased psychosocial stress, and waning as stressors decline.13 Patients with GAD often have chronically high levels of stress hormones that aggravate and complicate all other coexisting medical conditions.14 The disorder has a lifetime prevalence of 5.7% and involves near global worry about a wide range of features in the person’s life.1 These include issues that family members and clinicians recognize as mundane in the overall scheme of things, such as having difficulty choosing what to wear or fretting over whether a comment, a gift or a gesture was well received. GAD has even been described in lay terminology as “the worry sickness.” Patients themselves often recognize that their worry is excessive and that it interferes with their overall happiness and ability to function in productive ways in interpersonal, social, and work settings.
Patients with GAD generally do not present early in the course of their illness. They typically present after making repeated attempts to cope but failing to bring their emotional and physical symptoms under control. Patients will describe feeling physically and emotionally “drained,” which also leads to further feelings of depression and demoralization as their worries expand and their social and occupational functioning suffers. Not surprising is that anxiety and depression often coexist. In the physical examination, patients’ heart rates are frequently elevated in the mild range, and the symptom that adds greatly to their misery is muscle tension. Patients frequently describe feeling “tied up in knots.” Typically, the examination of the muscles in their neck, shoulders, and back reveal areas of localized tension. If long-standing, these areas of chronic muscle spasm may have a hard and “ropey” feel and are tender to palpation. Finally, patients with GAD appear both fatigued and distressed. The fatigue they feel is often from the combination of both their psychomotor restlessness and built-up sleep deprivation from insomnia. DSM-5 criteria are listed in Table 5-3.6
Contemporary primary care practices are busy and efficiency is very important. Since complaints of anxiety and depression are so common, it is helpful to utilize screening tools the patients may complete prior to seeing you. For anxiety, one of the best and most efficient screening instruments is the Generalized Anxiety Disorder Questionnaire-7 (GAD-7), summarized in Table 5-4.15 It consists of 7 symptom complexes that are consistent with the DSM-5 criteria with the patients rating how frequently they experience each feature and the extent of the difficulty. The clinician can review the areas checked. This facilitates a more efficient evaluation of the patient’s history as well as focusing on specific symptom-relief when developing the treatment plan. A score of 10 or more is the recommended cutoff that warrants further evaluation. As well, the GAD-7 should be administered at each follow-up visit to monitor the effectiveness of the treatment plan.
|Over the last 2 weeks, how often have you been bothered by the following problems?|
Not at all
More than half the days
Nearly every day
|Feeling nervous, anxious, or on edge|
|Not being able to stop or control worrying|
|Worrying too much about different things|
|Being so restless that it is hard to sit still|
|Becoming easily annoyed or irritable|
|Feeling afraid as if something awful might happen|
|Add the score from each column|
|Add column scores =||Total Score =________.|
Because patients so commonly complain of both anxious and depressive symptoms together, we recommend that both the PHQ-9 (see Chapter 4) and the GAD-7 be a component of routine patient screening, especially when a mental disorder is a possibility. Both screening instruments are available in the public domain and are easily accessed online—or may be copied from this book.
After initial review of the GAD-7, the patient-centered interview begins by starting with open-ended questions. The term “describe” is always a useful start when beginning the patient’s history; for example, “Describe the kinds of worries that bother you.” More helpful specific questions include “Would you or others describe you as a nervous person?” A developmental question is also useful: “Would your parents or relatives you grew up with describe you as a ‘worrier’ or perhaps a ‘worry-wart’?” The clinician should then inquire about the specific areas checked in the GAD-7.
We now address the details of pharmacological treatment, the mainstay for the clinician managing all anxiety disorders, especially GAD. First-line pharmacologic treatment for GAD is summarized in Table 5-5 and includes the very same SSRI and SNRI antidepressant medications you read about in Chapter 4.16 Note, however, that the starting doses are one-half those used for depression. These newer agents are efficacious and, since treatment will be long term for full recovery/remission, they have the least risk for side effects. Although tolerance also can sometimes be a problem with the newer agents,17 the severity and extent of the tolerance and habituation often seen with benzodiazepines does not occur. The general strategies include a starting dose with gradual upward titration guided by experience of adverse effect and the trajectory of improvement. The following SSRIs and serotonin–norepinephrine reuptake inhibitors (SNRIs) have FDA approval for the treatment of GAD.
|Antidepressant Medications||Antidepressant Side Effects|
|Class||Initial Dosea (mg/d)||Therap Dose (mg/d)||Half-Life||Sedation||Weight Gain||Sexual||Cardiac||Anticholinergic||Seizures||Drug Interactionb|
2D6 inhibitor +/−
At high doses only
2D6 inhibitor 4+
Incr. flecainide and β-blocker level
|−||−||Incr. flecainide level|
|−||−||Incr. flecainide level|
2D6 inhibitor 4+
Incr. flecainide and β-blocker level
|Venlafaxine XR (Effexor XR)||37.5||75-225||Short||−||+/−||+++||Increased BP and heart rate||−||−||Decr. indinavir level|
|Duloxetine (Cymbalta)||20||30-60||Short||−||+/−||+++||+/−||−||−||2D6 inhibitor 1+|
|1. Duloxetine (SNRI)||Starting dose: 20 mg qd.||Titrate up to 30-60 mg/d|
|2. Escitalopram (SSRI)||Starting dose: 5 mg qd.||Titrate up to 10-20 mg/d|
|3. Paroxetine (SSRI)||Starting dose: 10 mg qd.||Titrate up to 20-40 mg/d|
|4. Venlafaxine (SNRI)||Starting dose: 37.5 mg qd.||Titrate up to 75-225 mg/d|
Other SSRIs also effective and used as “off-label” treatment for GAD are citalopram, fluoxetine, and sertraline.
Generally, the same trial-times and therapeutic doses for treating depressive disorders apply in the treatment of anxiety disorders, as described for depression in Chapter 4. Because these medications may initially worsen anxiety (due to their stimulating qualities); however, we recommend starting at half the depression doses; the same reduction applies to those over 60 years old where the therapeutic dose is also reduced by one-half.
These new antidepressant medications are “first-line” because of their milder adverse-effect profiles but patients must still be cautioned to be alert and report adverse experiences. Venlafaxine has been demonstrated to elevate blood pressure as an adverse effect.18 Since other medications are equally effective in the treatment of GAD, venlafaxine should be avoided in patients with hypertension.
Common adverse-effects were reviewed in Chapter 4; to summarize, they include
Initial/early activation: Some patients experience an early significant increase in their anxiety that commonly results in nonadherence/noncooperation. This is usually dose-dependent and diminishes with reassurance, time, and patience—the therapeutic relationship is paramount in conveying this as one reduces the dose. Short-term use of a benzodiazepine (described later), for no more than 2 to 4 weeks, may be necessary to assist patients through this phase of treatment.
Sedation: Sedation is occasionally a problem, in which case the dosage is reduced or a less sedating antidepressant is used.
Weight increase: Many of the SSRIs are associated with weight gain, which can compound the patient’s anxiety. Switching to (or starting with) an SNRI like duloxetine usually suffices.
Cardiac effects: Aggravation of hypertension and enhancement of arrhythmias can occur with SNRIs like venlafaxine, so where this is a concern, one begins with an SSRI.
Sexual side effects: Most common are delayed ejaculation and orgasm. These are also dose-dependent—but do not improve over time. Use of medications for erectile dysfunction like sildenafil, tadalafil, and vardenafil is indicated in these circumstances. Both depressive and anxiety disorders themselves diminish libido and impair satisfying sexual function. Restoring sexual functioning is an important component of successful treatment.19
Gastrointestinal discomfort: The most common patient complaints are nausea and frequent loose stools/diarrhea, while others may develop constipation. These are also dose-dependent but decrease over time.
Discontinuation syndrome: Once on an SSRI or SNRI for 4 to 6 weeks, they should not be stopped abruptly. When they are, the patient may develop a withdrawal syndrome characterized by acute anxiety and depression, headaches, nausea, vomiting, diarrhea, vertigo, insomnia, paresthesias, tremors, and ataxia. Albeit distressing to patient and clinician alike, this withdrawal phase passes in a few days with supportive measures and re-administering a short-acting antidepressant.
Serotonin syndrome: This side effect occurs from excessive doses of serotonin-containing antidepressants, usually when given together or sequentially without an adequate washout period (see Table 5-6 for a summary and see Table 5-7 for switching antidepressants).