Anxiety is a common symptom in HIV-infected patients. When anxiety symptoms are severe or persistent, patients may have an anxiety disorder. These disorders include panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder (PTSD) (see Chapter 9: Trauma and Post-Traumatic Stress Disorder in Patients With HIV/AIDS). A recent study has shown that among HIV-infected patients receiving medical care, 20.3% have an anxiety disorder, with 12.3% meeting the criteria for panic disorder, 10.4% for PTSD, and 2.8% having generalized anxiety disorder.1 Patients with other psychiatric disorders, such as adjustment disorders, major depression, psychosis, or substance use disorders, can also present with significant anxiety. To help patients receive optimal care, clinicians need to be aware of the differences among these specific disorders. Furthermore, patients with histories of anxiety or mood disorders are susceptible to recurrence of anxiety symptoms during the course of HIV illness.

Key Point: Patients with limited social support may be particularly susceptible to developing anxiety symptoms.

I. CLINICAL PRESENTATION RECOMMENDATION: Clinicians should consider the diagnosis of an anxiety disorder when a patient presents with common somatic symptoms, such as chest pain, diaphoresis, dizziness, gastrointestinal disturbances, and/or headache, for which no underlying medical etiology can be established. Anxiety can present with a wide range of physiological manifestations, such as shortness of breath, chest pain, racing/pounding heart, dizziness, diaphoresis, numbness or tingling, nausea, or the sensation of choking. When patients present with these somatic symptoms, for which no underlying medical etiology can be established, clinicians should consider an anxiety disorder as the cause. In addition to somatic complaints, patients with anxiety disorders often present with fear, worry, insomnia, impaired concentration and memory, diminished appetite, ruminations, compulsive rituals, and avoidance of situations that make them anxious. The following questions may help clinicians determine whether anxiety is present: · Are you anxious? · Are you fearful or afraid? · Do you worry a lot? · Are you tense or irritable? · Are you restless? · Do you have difficulty sleeping?


II. DIAGNOSIS A. Diagnosis Anxiety symptoms such as worry, nervousness, fear, and tension are commonly experienced by people with HIV during periods of their illness and may be a response to stressful situations. An anxiety disorder occurs when symptoms: · Interfere with a patient's daily function (e.g., the patient is unable to work, leave home, attend to medical care) · Interfere with personal relationships · Cause marked subjective distress Even brief episodes of anxiety, such as those occurring during a panic attack, may interfere markedly in a patient's life and may warrant a diagnosis of an anxiety disorder. B. Differential Diagnosis 1. Other Mental Health Disorders and Medical Conditions RECOMMENDATIONS: Clinicians should exclude other mental health disorders in patients who present with anxiety. Clinicians should exclude medical conditions, including HIV-related central nervous system disease, in patients who present with anxiety. Clinicians should review medication regimens and substance use history in patients with anxiety.

Anxiety-like symptoms may also be caused by mental health disorders other than anxiety disorders. For example, it may be difficult to distinguish depression with agitation from an adjustment disorder with anxious mood. In general, adjustment reactions follow a stressful event, which is often not true in clinical depression, and are less likely to present with the entire vegetative symptom complex seen in depression, which is characterized by insomnia, diminished appetite, diurnal variation in mood, loss of pleasure/interest, feelings of guilt, fatigue, and attention and concentration problems. Underlying medical conditions may also cause anxiety-like symptoms. Clinicians should exclude medical etiologies when evaluating patients who present with these symptoms. Patients can present with anxiety-like symptoms due to any one of the following conditions: · · · · · · CNS pathologies: HIV-related infections, neoplasms, dementia, or delirium Systemic or metabolic illness: hypoxia, sepsis, electrolyte imbalance Endocrinopathies: thyroid disease, hypoglycemia, pheochromocytoma, Cushing's syndrome Respiratory conditions: pneumonia Cardiovascular conditions: arrhythmias, pulmonary embolus Substance intoxication/withdrawal: from alcohol, nicotine, caffeine, cocaine, and amphetamines


In addition, psychotropic medications and other commonly prescribed medications may cause anxiety-like symptoms (see Table 1). Intoxication or withdrawal from substances such as alcohol, nicotine, caffeine, cocaine, and amphetamines can also cause anxiety.

Table 1 Medications That May Cause Anxiety-Like Symptoms in HIV-Infected Patients

Category Antihypertensives Reserpine Hydralazine Isoniazid Cycloserine Most antipsychotic and antidepressant medications. Bupropion, an antidepressant that is also given for smoking cessation, makes some patients extremely anxious. Ephedrine Epinephrine Dopamine Phenylephrine Phenylpropanolamine Pseudoephedrine See the Adult HIV Guidelines, Chapter 4A: Antiretroviral Therapy, Appendix A Amphetamine and methylphenidate Digitalis Lidocaine Monosodium glutamate Nicotinic acid Procarbazine Steroids Theophylline and aminophylline Thyroid preparations Medication

Antituberculous agents





2. Anxiety Disorders Once an underlying medical etiology or substance/medication-induced cause has been excluded, a structured approach is helpful in distinguishing among the anxiety disorders (see Figure 1).



Yes Anxiety likely due to a general medical condition, substance, or medication

Underlying medical, substance, or medication etiology? Yes


Discrete episodes of intense anxiety/fear with chest pain, pounding heart, diaphoresis, shortness of breath?

Fear/avoidance of certain situations, places, or objects?

Worrying/ ruminating about a variety of things for months or years?

Intrusive, disturbing thoughts or compulsive rituals?

History of a traumatic event continuing to cause great distress?

History of a stressful situation causing nervousness or upset?







Panic attacks or panic disorder


Generalized anxiety disorder

Obsessivecompulsive disorder

Event <1 month ago

Symptoms >1 month

Adjustment disorder with anxious mood

Acute stress disorder


Figure 1. Algorithm for distinguishing anxiety disorders.


III. MANAGEMENT OF HIV-INFECTED PATIENTS WITH ANXIETY DISORDERS RECOMMENDATION: Clinicians should refer patients with symptoms of anxiety to a psychiatrist for evaluation and possible ongoing treatment when: · Anxiety symptoms do not respond to standard pharmlogic treatment or basic supportive/behavioral interventions · The diagnosis of an anxiety disorder is difficult to establish · Anxiety is persistent or severe · Patients with obsessive-compulsive disorder have intrusive or disturbing thoughts or compulsive rituals that are poorly controlled with the current medication or that cause the patient marked subjective distress · Anxiety occurs in patients with a significant substance use history or in those who are actively using substances

A. Psychological/Supportive Intervention in the Primary Care Setting Certain anxiety symptoms can be effectively managed without the use of medication. There are also patients who prefer to avoid the use of psychotropic medication. Patients with mild anxiety symptoms that do not interfere with function may respond to supportive or behavioral interventions. Clinicians may find the following strategies helpful in such situations: · Expressing empathy · Educating patients about anxiety · Reassuring patients that anxiety is the cause of somatic symptoms experienced during panic attacks · Identifying the psychological factors that contribute to anxiety · Preparing patients for stressful situations and assisting in development of coping mechanisms · Teaching patients simple relaxation exercises. Slow, deep breathing with focus on inspiration and expiration of air can be helpful. Such exercises can be useful when patients practice for 1 minute three times a day, increasing to 5 minutes, if possible.

Key Point: Basic supportive and behavioral interventions are sufficient to alleviate anxiety in certain patients.

For patients with more severe anxiety, psychotherapy, specialized behavioral treatments such as cognitive-behavioral therapy, and/or medication may be required.


B. Pharmlogic Intervention in the Primary Care Setting RECOMMENDATION: Clinicians should be familiar with the safety profiles of medications used to treat anxiety and how these medications may interact with those used in the treatment of HIV disease (Appendix I). HIV-infected patients, especially those who are symptomatic, are more sensitive to medication side effects and may respond to lower dosages of anxiolytics. For these reasons, it is generally best to "start low and go slow" when prescribing medication. Furthermore, because patients are often receiving multiple medications, the potential for drug-drug interactions is great. Clinicians should be familiar with the safety profiles of medications used to treat anxiety and how these medications may interact with those used in the treatment of HIV disease (Appendix I). 1. General Principles in the Pharmlogic Treatment of Anxiety Disorders and Their Symptoms

No single medication will treat the spectrum of symptoms seen in patients with anxiety disorders. The following general principles will help determine the pharmlogic intervention that is most likely to be helpful (see Table 2). · Panic Attacks/Panic Disorder--In general, while symptomatic relief for patients experiencing panic attacks can usually be accomplished with the short-term use of benzodiazepines, selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice because they effectively prevent panic attacks from recurring. Given the morbidity associated with ongoing panic attacks, it is important to give prophylaxis to prevent recurrence. Venlafaxine is also effective in preventing panic attacks, as well as the tricyclic antidepressants, but the latter are limited in their usage due to their side-effect profiles and potential for drug-drug interactions. Generalized Anxiety Disorder--Patients with chronic anxiety, consistent with generalized anxiety disorder, may require long-term therapy with medication. Buspirone should be considered because it is an effective anxiolytic that has no potential for abuse, which is particularly important for patients with a history of substance use. The SSRIs and venlafaxine can also be effective in some patients with persistent anxiety. Although some patients may experience relief sooner, the onset of action of buspirone (3-6 weeks) and SSRIs (2-4 weeks) may necessitate the shortterm use of benzodiazepines; however, these should be used with caution, because of the potential for dependence in some patients. Adjustment Disorder--Short-term symptomatic relief may be helpful in some patients. A time-limited use (2-4 weeks) of benzodiazepines prescribed on a daily or as-needed basis can be effective. Post-Traumatic Stress Disorder--See Chapter 9: Trauma and Post-Traumatic Stress Disorder in Patients With HIV/AIDS. Insomnia--Insomnia is an important symptom to treat because it often causes impaired daily function. If an underlying medical etiology or chemical cause has been excluded, insomnia should almost always be considered a symptom of an underlying psychiatric disorder (major depression, adjustment disorder, generalized anxiety disorder, PTSD). Diagnosis and treatment of the underlying condition is essential and



· · ·

often results in resolution of the insomnia. Nonpharmlogic approaches to treating insomnia should be tried before prescribing medications. See Chapter Somatic Symptoms for recommendations on treating insomnia.

Table 2 Commonly Used Psychotropic Medications in the Treatment of Anxiety Disorders and Anxiety Symptoms Disorder or Symptom Medication or Medication Class Panic disorder SSRIs · Citalopram · Paroxetine · Escitalopram · Fluoxetine · Sertraline

Tricyclics · Nortriptyline · Desipramine Benzodiazepines · Lorazepam · Alprazolam Other · Generalized anxiety disorder · Doxepin · Imipramine · Clonazepam


Buspirone SSRIs (listed above) SSRIs (listed above) Other · Fluvoxamine · Clomipramine

Obsessive-compulsive disorder

· Venlafaxine

Adjustment disorder with anxious mood Insomnia*

Benzodiazepines (listed above) Zolpidem Benzodiazepines (listed above) and temazepam Other · Trazodone · Doxepin SSRIs (listed above) SSRIs (listed above) Benzodiazepines (listed above) Other · Venlafaxine · Tricyclics (listed above)

PTSD Major depression with significant anxiety

* Nonpharmlogic approaches should be attempted before treatment with medication. See Chapter Somatic Symptoms. Sertraline and paroxetine are the only FDA-approved medications for PTSD. However, all SSRIs (in the same doses used for depression) are helpful in treating symptoms of depression and anxiety. See Chapter 9: Trauma and Post-Traumatic Stress Disorder in Patients With HIV/AIDS. See Chapter 6: Depression and Mania in Patients With HIV/AIDS. 7

2. Treatment of Anxiety Disorders in Substance Users RECOMMENDATIONS: Primary care clinicians should coordinate with a psychiatrist and/or addiction specialist when managing anxiety disorders among patients with substance use disorders. A psychiatric evaluation of these patients should be performed. Clinicians should discuss the long-term risks of dependence, withdrawal, and abuse, as well as the intended course of treatment, with patients with substance use disorders or a history of substance use disorders before benzodiazepines or other controlled substances are used to treat an anxiety disorder. Clinicians should make the decision to withhold benzodiazepines on a case-by-case basis, weighing the risks and benefits for patients with substance use disorders. The treatment of patients with anxiety who have a substance use history or who are actively using substances poses a challenge for clinicians. Such patients are most effectively managed when treatment is coordinated with a psychiatrist/addiction specialist. Psychiatric evaluation should be recommended for such patients. In some cases, clinicians should defer initiating treatment until the evaluation is completed. Although most clinicians attempt to avoid the use of medications with potential for abuse, such as benzodiazepines and other controlled substances, such treatment is indicated in some clinical situations. In these cases, discussions about the long-term risks of dependence, withdrawal, and abuse and the intended course of treatment are necessary prior to initiation of medication. The decision to withhold benzodiazepines should be made on a case-by-case basis, weighing the risks and benefits. Furthermore, the risk of discontinuing or withholding benzodiazepines may have serious medical complications. Documentation in the medical record of the decision-making process is essential to ensure consistency and continuity of care. (See Chapter Substance Use and Mental Health in HIV-Infected Patients.)

REFERENCE 1. Vitiello B, Burnam MA, Bing EG, et al. Use of psychotropic medications among HIV-infected patients in the United States. Am J Psychiatry 2003;160:547-554.




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