Anxiety Disorders

Question 1

Alprazolam, Chlordiazepoxide, Clonazepam, Clorazepate

Diazepam, Lorazepam, Oxazepam

Answer 1

Anxiety Disorders
Anxiolytic Benzodiazepines
• Considered *1st line agents in many disorders (often in combination)
• Dependence and tolerance concerns
• Avoid in pregnancy
FDA approved indications:
• *Anxiety, but many used off-label for other indications such as *seizure disorders and sedation
MOA
• Benzodiazepines bind to GABAA receptors leading to increased binding of GABA at this receptor (enhances effect of GABA)
• All benzodiazepines have anxiolytic, sedative-hypnotic, anticonvulsant, and muscle relaxing properties
ADE
• *CNS depression most common, including occasional memory impairment
• Less common: disorientation, depression, confusion, irritability, aggression, excitement
Drug Interactions:
• *Additive adverse effects/ CNS depression
• *Some CYP interactions
• Lorazepam and oxazepam do NOT go through Phase 1 hepatic metabolism and not affected by P450 enzymes
ANTIDOTE
– *Flumazenil (Romazicon) is the “antidote” if too much benzodiazepines are used
• Benzodiazepine antagonist
• *Risk of seizures with use

Question 2

Antidepressants

Answer 2

Anxiety Disorders
• *SSRIs are most commonly used
• Some SNRIs used (venlafaxine most common)
• *TCAs used, but limited by adverse effects
• Considered *1st line agents for most disorders
• Typically, 4-12 weeks to take full effect
• Benefit in cognitive symptoms (worry) and, subsequently, physical symptoms will improve
MOA
• Mechanisms in anxiety not fully understood but likely related to *serotonin (+/- norepinephrine effects)
• Possibly due to improvement in *stress-adaptive pathways
• All thought to have comparable efficacy, but some differences have been found in clinical trials and use based on disorder

Question 3

Buspirone (Buspar)

Answer 3

Anxiety Disorders
Clinical effects:
• *2nd line agent when effective in the disorder
• Effective, but less than benzodiazepines
• Likely most benefit with *cognitive symptoms
• Onset of efficacy is about 2-6 weeks
FDA approved use:
• *Anxiety
MOA
• Unknown, thought to be related to 5-HT1A partial agonism
ADE
• *Much better tolerated than benzodiazepines
• Dizziness, nausea, headache, some GI effects
Drug Interactions
• Possible if combined with strong *3A4 inducer or inhibitor

Question 4

Gabapentin, tiagabine, and pregabalin

Answer 4

Anxiety Disorders
Anticonvulsants
MOA
• MOA vary, unknown how benefits anxiety (possibly GABA augmentation)
ADE
• *Somnolence, dry mouth, weight gain, cognitive impairment/slowing

Question 5

Hydroxyzine (Vistaril), diphenhydramine (Benadryl)

Answer 5

Anxiety Disorders
Antihistamines
o Patients may self-medicate with OTCs
o Hydroxyzine very popular in psychiatric patients and when want to avoid benzodiazepine
Clinical effect:
• May be used as *alternatives to benzodiazepines for short-term treatment (or try prior to benzo)
• Long term treatment limited by adverse effects
MOA
• Mechanism of benefit in anxiety: unknown
ADE
• *Sedation, anticholinergic effects

Question 6

Clonidine, prazosin, propranolol

Answer 6

Anxiety Disorders
Anti-adrenergics
• Clonidine (α2 agonist)
- prazosin (α1 antagonist)
- propranolol (β-blocker)
Clinical effect:
• Less effective than benzodiazepines
• For somatic symptoms (physical response to anxiety)
MOA 
• MOA related to decrease in physical response to anxiety resulting from *release of NE 
ADE
- *DEC BP