Anxiety Disorders

Question 1

Clinical Presentation of Generalized Anxiety Disorder

Answer 1

1) Excessive anxiety and uncontrolled worry
2) Feeling on edge, poor concentration
3) Restlessness, fatigue, muscle tension
4) Difficulty sleeping, irritability
5) Impairment in social or occupational functioning

Question 2

Clinical Presentation of Obsessive-Compulsive Disorder

Answer 2

1) Obsessions: recurrent thoughts, images, and/or impulses

2) Compulsions: Repetitive activities and/or mental acts that reduce the anxiety caused by the obsessions

Question 3

Clinical Presentation of Panic Attack/Disorder

Answer 3

1) Physical Symptoms: Chest pain or discomfort, dizziness, shortness of breath, tachycardia, tremor, nausea, palpitations, sweating
2) Psychological: Fear of losing control or dying, fear of ability to escape from fearful situations
Agoraphobia may result from repeated panic attacks

Question 4

Clinical Presentation of Posttraumatic Stress Disorder

Answer 4

Triad of symptom complexes:

1) Reexperiencing: Flashbacks of the event, recurring and disturbing memories or dreams
2) Avoidance: Avoiding thoughts, feelings conversations, people, or activities related to the event: inability to recall the event; avoiding others (isolating); sense of a foreshortened future
3) Hyperarousal: Decreased concentration, insomnia, irritability, easily startled, Hypervigilance

Question 5

SSRIs in Anxiety Disorders

Answer 5

1) 1st line in all anxiety disorder
2) onset in 2 weeks… Full effect 6 weeks
3) agitation and irritability common adverse events.. Start low and go slow and council
4) starting dose:
Paroxetine - 10mg
Citalopram - 10mg
Sertraline - 25mg
5) fluoxetine has higher risk of agitation and anxiety, therefore not drug of first choice but start at 5mg
6) Withdrawal syndrome with abrupt discontinuation. More common with shorter t1/2 drugs

Question 5

Clinical Presentation of Social Anxiety Disorder

Answer 5

1) Fear of being embarrassed, humiliated, or evaluated by others
2) Fear of situations: Speaking, eating, or interacting in a group of people or with authority figures; public speaking; taling with strangers
3) Physical symptoms: GI upset - Diarrhea; sweating, flushing, tachycardia, tremor

Question 6

SNRI in Anxiety Disorders

Answer 6

1) FDA approved for GAD, panic disorder and social anxiety disorder
2) useful alternative to SSRI therapy
3) Venlafaxine and duloxetine have most clinical evidence of efficacy
4) lower dose than for depression:
Duloxetine 30mg
Venlafaxine 37.5 mg

Question 7

TCAs in Anxiety Disorder

Answer 7

1) imipramine and clamor amine have the best evidence base, specifically panic disorder and OCD respectively
2) effective but limited by side effects: anticholinergic effects, sexual dysfunction, and toxicity in overdose.

Question 8

Monoamine oxidase inhibitors (MAOIs) in Anxiety Disorders

Answer 8

i. Phenelzine is well studied in GAD.
ii. Use is limited by dietary requirements as well as adverse effects.
iii. Reserved for third- or fourth-line therapy

Question 9

Novel Antidepressants in Anxiety Disorders

Answer 9

i. Small clinical trials have observed some efficacy of mirtazapine in obsessive-compulsive disorder and panic disorder.
ii. Limited efficacy of mirtazapine in PTSD, with no controlled trials of its use in GAD
iii. Mixed findings for bupropion in anxiety disorders

Question 10

Anticonvulsants In Anxiety Disorders

Answer 10

a. Pregabalin
i. Effective for short-term treatment of GAD, not FDA approved
ii. Adverse effects include somnolence, dizziness, edema, and dry mouth.
iii. Schedule V controlled substance – Addiction potential noted in clinical trials
b. Gabapentin
i. Not FDA approved for the treatment of GAD, but clinically, may be used for anxiety, especially if there is also neuropathic pain
ii. Available as a generic, but is dosed more frequently, two or three times daily
c. Topiramate
i. Studied in PTSD for augmentation therapy, mixed results
ii. Cognitive adverse effects necessitate slow-dose titration.
d. Other anticonvulsants
i. Limited evidence of efficacy of lamotrigine, tiagabine, valproate, or carbamazepine in anxiety disorders as monotherapy
ii. Studied for augmentation therapy; no efficacy shown for monotherapy

Question 11

Atypical Antipsychotics in Anxiety Disorders

Answer 11

a. Risperidone, quetiapine, and olanzapine have limited evidence of efficacy as augmenting agents in GAD.
b. Conflicting evidence for risperidone and olanzapine use in PTSD as augmenting agents for patients with reexperiencing or hyperarousal symptoms; may be useful if prominent psychosis
c. A recent study of adjunctive risperidone in military veterans did not show efficacy of risperidone on the core symptoms of PTSD, or other outcomes, including quality of life, depression, or anxiety.
d. Concern for metabolic adverse effects, including weight gain

Question 12

Azapirones – Buspirone in Anxiety Disorders

Answer 12

a. FDA approved for the treatment of GAD
b. Clinical trials do not show consistent efficacy in other anxiety disorders.
c. Onset of effect in 2 weeks; delay in onset can be an adherence issue in patients with past use of benzodiazepines and an expectation of rapid relief
d. In general, well tolerated; adverse effects include nausea, headache, and dizziness
e. Usual initial dose is 7.5 mg orally twice daily; usual dose range is 15–60 mg/day.
f. Minimal drug interaction; is a cytochrome P450 (CYP) 3A4 substrate

Question 13

Hydroxyzine in Anxiety Disorders

Answer 13

a. May be useful in performance-related social anxiety disorder
b. Propranolol most commonly used (10–80 mg per dose) or atenolol (25–50 mg per dose) taken 1–2 hours before performance
c. Decrease physiologic effects of nervousness – Tremor, blushing, increased heart rate (HR)

Question 14

Prazosin/clonidine in Anxiety Disorders

Answer 14

a. The α1-adrenergic antagonist prazosin and the α2-agonist clonidine are commonly used in PTSD to treat nightmares associated with reexperiencing symptoms.
b. Prazosin in initial doses of 1–2 mg orally at bedtime and clonidine 0.1 mg/day may be useful.
c. Meaningful doses of prazosin to treat nightmares or night terrors should approach 10 mg/day for efficacy.
d. Clonidine doses are initially 0.1 mg once nightly at bedtime.
e. Orthostatic hypotension should be monitored.

Question 15

Benzodiazepines in Anxiety Disorders

Answer 15

a. All benzodiazepines are effective for the treatment of GAD.
b. Alprazolam shows the greatest efficacy for panic attacks and panic disorder; evidence of usefulness of clonazepam, lorazepam, and diazepam
c. Benzodiazepines can be useful in social anxiety disorder, with evidence for reduced relapse.
d. Overall, benzodiazepine use should be avoided in PTSD because of the high risk of substance use in this population.
e. Benzodiazepines have shown limited efficacy in obsessive-compulsive disorder.
f. Rapid relief of anxiety symptoms is seen with benzodiazepines, leading to the combination acute use of these drugs with longer-term therapy, including use with SSRIs, SNRIs, and TCAs.
g. Tolerance and dependence, as well as risk of toxicity in overdose, have limited use by some prescribers.
h. Use should be avoided in patients with a history of, or current, substance abuse or dependence.
i. Benzodiazepines are not useful for the treatment of depression and may contribute to or exacerbate depressive symptoms with long-term use.
j. Active metabolite (N-desmethyldiazepam) for some drugs accumulates to contribute to hangover effect.
k. Avoid use in the elderly.
l. Central nervous system (CNS) adverse effects: Drowsiness, sedation, ataxia, confusion, irritability, paradoxical excitement, and decreased concentration and recall
m. Discontinuation of benzodiazepine therapy should be slow to avoid rebound anxiety as well as withdrawal seizures.
n. If therapy lasts more than 1 year, taper over 2–4 months.
o. Consider changing to longer-acting benzodiazepine (diazepam, clonazepam, chlordiazepoxide) during the taper to discontinuation to decrease the risk of withdrawal effects and to reduce the doses per day.

Question 16

Alternative Therapies in Anxiety Disorders

Answer 16

a. Kava
i. Herbal therapy has been studied for anxiety disorders, but clinical trials have shown no benefit.
ii. Standardized dietary extracts used in a dose of 100 mg orally three times/day
iii. Hepatotoxicity and liver failure reported; use is not recommended
iv. May aggravate symptoms of Parkinson disease.
v. Because of possible inhibition of cyclooxygenase and decrease in thromboxane A2 production, platelet aggregation may be inhibited.

b. Valerian
i. Believed to have properties similar to benzodiazepines
ii. Little controlled evidence of efficacy
iii. Avoid use in pregnancy.
iv. There have been reports of liver toxicity, including life-threatening liver damage.

c. Passionflower
i. Folk remedy for anxiety and insomnia
ii. No published trials of efficacy
iii. In general, well tolerated but can cause dizziness, ataxia, and confusion

Question 17

Therapy Summary and Patient Counseling in Anxiety Disorders

Answer 17

1. Patients may have long-standing anxiety disorders before presenting for treatment.
2. Somatic disorders are often the reason for the clinic visit; evaluate for underlying anxiety as part of the treatment plan.
3. Serotonergic agents are first-line therapy for the treatment of anxiety disorders.
4. Onset of effect in the first few weeks of treatment; may be several weeks before full effect of a specific drug and dose
5. Benzodiazepines are effective agents for GAD, and they may be used as “bridge therapy” in the short term in combination with serotonergic agents.
6. Withdrawal effects are common with abrupt discontinuation; counsel patient on the need to adhere to therapy to avoid them.
7. Full effects of therapy may not include complete resolution of symptoms.
8. Counsel patient to avoid the use of other CNS depressants in combination with benzodiazepines, including alcohol.
9. Take a complete substance-use and substance-abuse history.
10. Encourage patient to seek psychotherapeutic options for treatment.

Question 18

FDA Approved for Generalized Anxiety Disorder

Answer 18

paroxetine
escitalopram
venlafaxine XR
duloxetine
buspirone
benzodiazepines 
hydroxyzine

Question 19

FDA Approved for Panic Disorder

Answer 19

fluoxetine
sertraline
paroxetine
venlafaxine XR
clonazepam
alprazolam

Question 20

FDA Approved for PTSD

Answer 20

paroxetine

sertraline

Question 21

FDA Approved for Obsessive-compulsive disorder

Answer 21

fluoxetine
fluvoxamine
paroxetine
sertraline
clomipramine

Question 22

FDA Approved for Social Anxiety Disorder

Answer 22

paroxetine
sertraline
venlafaxine