Anxiety Disorders

Background

Anxiety symptoms are common and can develop or recur for many reasons, including a patient's worries about HIV infection and treatment, or issues unrelated to HIV. Symptoms can range from mild distress to full-blown anxiety disorders. Symptoms of anxiety can mimic symptoms of physical illness, and an appropriate workup should be performed to rule out other illnesses. Use of illicit drugs (e.g., amphetamines, cocaine) or alcohol can cause or substantially worsen anxiety symptoms; all patients should be screened for substance use.

Anxiety disorders include generalized anxiety disorder, specific phobia, and social phobia; related disorders include posttraumatic stress disorder (PTSD) and panic disorder. This chapter focuses primarily on anxiety symptoms and generalized anxiety disorder. See chapters Panic Disorder and Posttraumatic Stress Disorder for further information about these conditions.

S: Subjective

The criteria for a diagnosis of generalized anxiety disorder include unrealistic or excessive worry about two or more life circumstances for ≥6 months, and at least three of the following subjective complaints:

  • Restlessness or feeling keyed-up or on edge
  • Difficulty concentrating or mind going blank
  • Irritability
  • Muscle tension
  • Being easily fatigued
  • Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep)

Other subjective complaints may include the following:

  • Shortness of breath or smothering sensations
  • Palpitations or accelerated heart rate
  • Dizziness or lightheadedness
  • Exaggerated startle response
  • Trembling, twitching, or feeling shaky
  • Dry mouth
  • Flushes or chills
  • Frequent urination
  • Muscle aches or soreness
  • Nausea, diarrhea, or other abdominal distress
  • Skin rashes
  • Sweating or cold, clammy hands
  • Trouble swallowing or "lump in the throat"

Ask about the symptoms indicated above, and about the following:

  • Anxiety patterns (e.g., constant or intermittent; timing, duration, precipitants)
  • Onset: sudden or gradual
  • Caffeine intake
  • Recreational drug or alcohol use (current
    or recent)
  • Concomitant illnesses (e.g., cardiac, pulmonary, endocrine)
  • Family history of similar problems
  • Medications, supplements, and herbal preparations
  • History of previous episodes
  • Recent stressors
  • Sleep disturbances
  • Other physical symptoms

O: Objective

Measure vital signs, with particular attention to heart rate (tachycardia) and respiratory rate (shortness of breath, hyperventilation).

Perform a physical examination, including mental status and neurologic, cardiopulmonary, and thyroid examinations.

A: Assessment

A differential diagnosis may include the following medical conditions:

  • Substance use (e.g., amphetamines, cocaine)
  • Substance or medication withdrawal (e.g., alcohol, benzodiazepines)
  • Excessive caffeine intake
  • Electrolyte imbalances
  • Heart disease, arrhythmias
  • Hyperthyroidism
  • Hypoglycemia
  • Immune disorders
  • Respiratory disease, hypoxia
  • Medication adverse effects (e.g., with efavirenz, isoniazid, corticosteroids, theophylline, or stimulants)
  • Sleep disturbances or sleep deprivation
  • Allergic reactions
  • Anemia
  • Central nervous system (CNS) or opportunistic infections or malignancies
  • Systemic or other infections
  • Vitamin B12 deficiency

P: Plan

Diagnostic Evaluation

Perform the following tests:

  • Blood glucose, electrolytes
  • Thyroid function tests (TSH, T4)
  • Electrocardiogram (EKG) if patient has shortness of breath or palpitations
  • Arterial blood gases (if difficulty breathing is not self-limited)
  • Other tests as indicated by symptoms and physical examination

Treatment

Once medical disorders have been ruled out, and the diagnosis of an anxiety disorder is established, several options are available:

Psychotherapy

Options include cognitive-behavioral therapy, interpersonal therapy, exposure therapy, a stress-management group, relaxation therapy, visualization, guided imagery, supportive psychotherapy, and psychodynamic psychotherapy. Long-term psychotherapy may be indicated if experienced professionals are available and the patient is capable of forming an ongoing relationship. If possible, refer to an HIV-experienced therapist. The type of psychotherapy available to the patient often depends on the skills and training of the practitioners in a given health care system or region. In addition, the patient may be referred to available community-based support.

Pharmacotherapy

Medications, with or without psychotherapy, may alleviate symptoms of anxiety. Patients with advanced HIV disease, like geriatric patients, may be more vulnerable to the CNS effects of certain medications. Medications that affect the CNS should be started at low dosage and titrated slowly. Similar precautions should apply to patients with liver dysfunction.

Antidepressants

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are effective in treating patients with anxiety. They are favored for long-term use when a specific anxiety disorder is present and persistent. These medications do not cause tolerance or pose a risk of addiction. Below is a list of antidepressants approved by the U.S. Food and Drug Administration (FDA) for specific anxiety disorders, and their usual recommended dosages. FDA recommendations are based on availability of specific study data, but all SSRIs (regardless of whether they have an FDA indication for anxiety) may be helpful for a broad range of anxiety disorders.

Common adverse effects of SSRIs and SNRIs include sexual dysfunction, sleep disturbance, and nausea. For patients who are medically ill, these medications should be started at low dosage and titrated up slowly; a low dosage may be effective. These medications also should be down-tapered slowly; SSRI/SNRI discontinuation syndrome may occur if they are discontinued abruptly.

See chapter Major Depression and Other Depressive Disorders for further information about antidepressant medications, including adverse effects.

SSRI antidepressants:

  • Fluoxetine (Prozac): FDA indication for panic disorder with a recommended dosage of 20 mg QD. Also recommended for obsessive-compulsive disorder, but higher dosages are needed, sometimes up to 80 mg daily.
  • Escitalopram (Lexapro): FDA indication for generalized anxiety disorder at a dosage of 10 mg QD.
  • Citalopram (Celexa): Does not have specific FDA indications for anxiety disorders. Suggested dosage: start at 10 mg QD and titrate as needed; maximum dosage: 60 mg daily.
  • Paroxetine (Paxil): FDA indications for obsessive-compulsive disorder and panic disorder both at a recommended dosage of 40 mg QD. Also indicated for social anxiety disorder at a dosage of 20-40 mg daily. Usual starting dosage: 10 mg daily.
  • Sertraline (Zoloft): FDA indications for panic disorder and PTSD at dosages of 50-200 mg QD. Usual starting dosage: 25 mg daily.

SNRI antidepressants:

  • Venlafaxine timed-release formulation (Effexor XR): FDA indication for generalized anxiety disorder, at recommended dosages of 75-225 mg per day. Note: There is a risk of hypertension at the higher dosages of venlafaxine; monitor blood pressure.
  • Duloxetine (Cymbalta): FDA indication for generalized anxiety disorder at a recommended dosage of 60 mg QD.

Other antidepressants:

  • Some sedating antidepressants are effective, nonaddictive agents that are helpful when taken at bedtime for both insomnia and anxiety symptoms. These include trazodone 25-100 mg QHS or imipramine (Tofranil) 25 mg QHS. Note that imipramine and other tricyclics must be used with caution but are not contraindicated for use by patients taking ritonavir (including ritonavir-boosted protease inhibitors [PIs]).
  • Gabapentin (Neurontin), which sometimes is used as a mood stabilizer, may be given at dosages of 200-400 mg BID to QID and may help to diminish anxiety.

Anxiolytics

Short-term use of benzodiazepines sometimes is appropriate for mild and brief situational anxiety symptoms, even without the presence of a specific anxiety disorder. For longer-term use, non-benzodiazepines (e.g., buspirone [see below], SSRIs, or SNRIs) are preferred.

  • Buspirone (BuSpar) is a nonaddictive anxiolytic. Start at 5 mg PO TID. If symptoms persist, the dosage can be increased by 5 mg per dose each week to a maximum of 10-15 mg TID (for a total daily dosage of 30-45 mg). It will take several weeks for patients to notice a decrease in anxiety; low-dose benzodiazepines may be used during this interval. The major potential adverse effects of buspirone are dizziness and lightheadedness.
  • Consider intermediate half-life benzodiazepines such as lorazepam (Ativan) 0.5 mg PO Q8H or oxazepam (Serax) 10 mg PO Q6H if buspirone is not tolerated or to alleviate anxiety symptoms until buspirone takes effect. Longer-acting benzodiazepines such as clonazepam (Klonopin) also may be useful at dosages of 0.25-0.5 mg PO BID.
  • Benzodiazepines generally should be used only for acute, short-term management because of the risk of tolerance and physiologic dependence. These risks are even more problematic for patients with a history of addiction.

Potential ARV Interactions

Interactions may occur between certain ARVs and agents used to treat anxiety. Some combinations may be contraindicated and others may require dosage adjustment. Refer to medication interaction resources or consult with an HIV clinical pharmacist, HIV specialist, or psychiatrist before prescribing.

Antidepressants

  • Some ARV medications (particularly PIs) and the pharmacokinetic booster cobicistat may affect the metabolism of some antidepressants via cytochrome P450 interactions. For most SSRIs and SNRIs, interactions with ARVs generally are not clinically significant; in the case of tricyclics, their levels may be significantly increased by ritonavir. On the other hand, some PIs may decrease levels of paroxetine and sertraline, and efavirenz also lowers sertraline levels. See chapter Major Depression and Other Depressive Disorders for further information.

Anxiolytics

  • PIs, nonnucleoside reverse transcriptase inhibitors (NNRTIs), and cobicistat may raise blood concentrations of many benzodiazepines. Consider using a benzodiazepine metabolized by glucuronidation (e.g., lorazepam, oxazepam), particularly in patients with liver disease. For benzodiazepines metabolized by the CYP system (e.g., clonazepam), start at low dosages and titrate slowly. Given the very long half-life of both the parent drug and its metabolites, diazepam is best avoided in patients receiving ART. Other CNS depressants and alcohol should be avoided in patients taking these benzodiazepines.
  • Midazolam (Versed) and triazolam (Halcion) are contraindicated for use with all PIs and with cobicistat, delavirdine, and efavirenz.
  • Buspirone levels may be increased by ritonavir-boosted PIs and cobicistat, and may be decreased by CYP inducers. Monitor patients for adverse effects and for efficacy.

Patient Education

  • Behavioral interventions can help to reduce anxiety, but may take practice. Patients should seek help from a therapist or another experienced source.
  • Advise patients that misuse of alcohol or illicit drugs can cause or substantially worsen anxiety symptoms; advise patients to decrease or eliminate use. Refer for substance abuse treatment if indicated.
  • Inform patients that they may develop problems with sexual function because of antianxiety medications. Patients should report any problems to their prescribers. (Note: Providers should let patients know that sexual well-being is fundamental to quality of life and can be talked about and addressed in the clinical setting.)

References