Exam 2 - Anxiety and Anxiety-Related Conditions

Learning Objectives

• Select appropriate therapy based upon patient-specific factors for Generalized Anxiety Disorder (GAD), Panic disorder (PD), PostTraumatic Stress Disorder (PTSD), ObsessiveCompulsiveDisorder (OCD)

• Identify correct therapeuticoption for GAD, PD, PTSD,OCD

• Compare risks and benefits of treatment for a specific patient

What is considered 1st line therapy for generalized anxiety disorder?

• Nonpharmacologic intervention

• SSRIs

• SNRIs

What are the first line SSRIs that are FDA approved for generalized anxiety disorder?

Paroxetine (Paxil)

Escitalopram (Lexapro)

What are the first line SNRIs that FDA approved for generalized anxiety disorder?

Venlafaxine (Effexor)

Duloxetine (Cymbalta)

How are SSRIs/SNRIs used in clinical practice?

Any SSRI or SNRI may be utilized

May start 50% of depression dose, then titrate slowly, therapeutic dose may be higher

What is Buspirone’s role in treatment of generalized anxiety disorder?

• May consider if unable to tolerate SSRI/SNRI

• Many clinicians/patients do not find as effective

What are clinical pearls of Buspirone (Buspar)?

• CANNOT DOSE PRN!! → Supposed to be given BID or TID

• 4-6 week onset of action (probably longer like SSRI or SNRIs)

• Minimal side effects, well tolerated (nausea, headache)

What are benzodiazepines’ role in treating generalized anxiety disorder?

Only for short term treatment of anxiety

• Acts as bandaid, doesn’t treat the source

What receptor do benzodiazepines bind to?

GABA_A receptor

Very similar to alcohol

What are pros/cons of benzodiazepine use?

Pros

• Very effective

• Rapid onset of action

Cons

• Substance of abuse (dependence vs. abuse vs. tolerance)

  • Tolerance is more of the issue, not really dependence

• Rebound anxiety → Anxiety comes back even harder than previously

• Risk of death in overdose (CNS and respiratory depression)

• Risk of drug interactions ➔ CNS or respiratory depression

What drug interactions do benzodiazepines have? (when should we NOT use)

Drugs interactions

• Additive CNS or respiratory depression with:

  • Opiates

  • Alcohol

  • Barbiturates

• CYP3A4 substrates: alprazolam, clonazepam, diazepam

What are clinical pearls of benzodiazepines?

Can cause rebound anxiety

They can be addictive substances (weigh out dependence vs abuse vs tolerance)

When/how SHOULD benzodiazepines be used?

• Used adjunctive to serotonergic agent (SSRI or SNRI)

• When to use:

  • If FAST onset is needed

  • If minimal improvement is seen

  • Chronic use is NOT required (avoid chronic use of benzos)

  • Patient doesn’t have substance use disorders (avoid in patients that do)

  • Patient is not on opiates (Do NOT use with concurrent opiates)

What side effects/ADRs are seen with benzodiazepines?

SideEffects/ADR

• Sedation, ataxia (risk of fall)

• Rare

  • Confusion, disorientation

  • Decreased ability to form new memories

  • Irritability, aggression, paradoxical excitation

  • Respiratory depression (more common with concurrent opiates)

How are benzodiazepines metabolized?

Most are hepatically metabolized and cleared

Caution use in hepatic injury/failure

Which benzodiazepines are NOT hepatically metabolized?

L O T

Lorazepam

Oxazepam

Temazepam

What is Hydroxyzine’s role in treatment of generalized anxiety disorder?

Appropriate alternative to benzodiazepines

• Monotherapy: antidepressants should be avoided (ex. Bipolar disorder)

• Use as adjunct to serotonergic agent (can be used as scheduled or PRN)

What kind of drug is Hydroxyzine (Vistaril)?

It is a H₁ Antagonist

What side effects are seen with hydroxyzine?

Sedation, some anticholinergic effects (dry mouth, constipation)

What other agents can be used for generalized anxiety disorder?

• Pregabalin (Lyrica) → Effective but expensive

  • Must be scheduled dosing

  • Down side: SEDATING

• Quetiapine (Seroquel)

  • Risks > Benefits, so rarely used

What are considered first and second line therapies in PANIC disorder?

First line:

• Non-pharmacologic therapies

• SSRIs

• Venlafaxine XR

Second Line:

• Benzodiazepines (may use if rapid symptom control is necessary for acute management)

How should SSRIs and Venlafaxine be started for panic disorder?

• If hypersensitive to jitteriness syndrome → Start ¼ to ½ of the depression starting dose and titrate slowly

• SSRIs and Venla are selected based on side effects, drug interactions, etc.

When are Benzodiazepines used for PANIC disorders?

• Typically used after failure of first line tx

• Helpful for anticipatory anxiety or when stat dose is needed

• May require higher doses than for GAD

• !!!Avoid monotherapy use!!!

What is considered our third line therapy for PANIC disorders?

TCAs - tricyclic antidepressants

• Comparable efficacy to SSRIs but less tolerated

• Effective for: reducing frequency of attacks (60%), severity of agoraphobic avoidance, overall anxiety and depression

Which TCAs are used for panic disorder? (3rd line)

Clomipramine

Imipramine

What is our LAST LINE of therapy for PANIC disorder?

Mirtazapine → very little data support use

MAOI (Phenelezine)

Both not used, idk if this is important to know

What is considered FIRST line for treatment of PTSD?

Trauma focused psychotherapy

What is considered second line therapy to treat PTSD and when should they be used?

SSRIs (Sertraline, Paroxetine)

SNRIs (Venlafaxine)

• Should be used if:

  • 1) Patient is unwilling or unable to engage in therapy

  • 2) Used adjunctive to therapy

Which agents should we AVOID use for treatment of PTSD?

• Antiepileptics (Divalproex, lamotrigine, carbamazepine, gabapentin)

• Antipsychotics (Olanzapine, Quetiapine, risperidone)

• TCAs and MAOIs

What is the specific role of Prazosin?

Used for PTSD nightmares

→ Only for traumatic event-related nightmares, not just any nightmares

What is the MOA of Prazosin?

Mechanism of Action

• α1receptor blockade

• α1receptors control startle and sleep responses

• Blockade improves sleep quality, decrease PTSD nightmares

How should Prazosin be dosed?

DO NOT USE PRN!

• think about it… how could you use a medication as needed for nightmares?

Which medications should be AVOIDED for PTSD?

Benzodiazepines

• May worsen recovery from trauma

What are first line options for treatment of obsessive compulsive disorder (OCD)?

• Non-pharmacologic therapy

• SSRIs (at very high dose)

Which SSRIs are used for OCD? How are they dosed?

• FDA Approved: Fluoxetine, Fluvoxamine, Paroxetine, Sertraline

• Non-FDA: Escitalopram

• Very high doses are often needed

What is the max allowed dose of Citalopram for OCD? (and how does it compare to max doses of depression)

Max dose in OCD = 120mg/day

Max dose in depression = 40mg (previously 80mg)

What is considered second line therapy for OCD?

• Another SSRI → Keep trying until options are exhausted

• Clomipramine (Tertiary TCA)

• Venlafaxine SR (not FDA approved)