In this section, we will discuss the pharmacotherapy of Generalized Anxiety Disorder, Panic Disorder, and Social Anxiety Disorder. For each disease state, we will go over symptoms, pharmacologic treatments, and adverse drug events for each treatment.

Epidemiology of Anxiety Disorders

Anxiety disorders are one of the most common psychiatric disorders. Being female, having a family history, or coming from certain socioeconomic background increase the risk of having anxiety disorders. Anxiety disorders are commonly to be comorbid with mood disorders, schizophrenia, dementia, depression (very common), and physical illness.

Remember: there is a big difference between normal anxiety and anxiety disorders if you want a quick review, head over to CNS 10.

Options for treatment include psychotherapy, pharmacotherapy, and education. Remember that psychotherapy, most times, is the first-line therapy. Psychotherapy is a very good add-on that improves the success rate of the treatment.

Physiological versus Psychological Symptoms

There are two types of symptoms when we consider anxiety disorders: physiological (somatic) and psychological.

What can we target in anxiety disorders?

1. Serotonergic system
   • This focuses on serotonin inhibitors like SSRI and SNRI
   • Targeting this help improve long-term psychological function
2. GABA-ergic system
   • This focuses on GABA potentiator like benzodiazepines
   • Targeting this will not fix the underlying issue, but it can help reduce the overexcited state temporarily.
3. Adrenergic system
   • This focuses on norepinephrine inhibition like SNRI or TCA.
   • Targeting this will help a lot with the sympathetic nervous system and reduce the physiological symptoms.

Psychotherapy and Education

Before we hop into the medications, I want to have a small section for psychotherapy and education.

Psychotherapy includes cognitive behavioral therapy (huge!), talk therapy, mindfulness meditation, bio-feedback.

Education includes avoiding harmful intake (alcohol, nicotine), exercise habits, sleep hygiene, and breathing exercise.

Generalized Anxiety Disorder

For a quick review of GAD DSM-5, go here to CNS 10:

Treatment goal: Remission (can be hard), and minimal functional impairment

Monitoring and Follow-up: Monitor every 2 weeks for improvement of anxiety symptoms and functioning. The rating scales used are HAM-A and GAD-7. To be considered a response is to have at least a 50% improvement.

Pharmacotherapy:

First-line: SSRI or SNRI

• All SSRIs or SNRIs can be used as first-line. The ones that are approved for GAD are venlafaxine, duloxetine, paroxetine, and escitalopram.
• Please note that some antidepressants can worsen anxiety, like fluoxetine and sertraline
• Physiological symptom relief: Not really, inconsistent
• Psychological symptom relief: Yes

Second-line: Try another SSRI or SNRI, or TCA

• Try another SSRI or SNRI agent, or consider trying TCA.
• TCA needs to be used with caution due to the narrow therapeutic index. Try to avoid elderly patients or patients with narrow-angle glaucoma or BPH.
  • Imipramine is the only TCA approved for GAD
• Physiological symptom relief: Not really, inconsistent
• Psychological symptom relief: Yes

Adjunctive: Adjunct SSRI/SNRI, buspirone, hydroxyzine, pregabalin, quetiapine, benzodiazepines

• Adjunct SSRI/SNRI include mirtazapine, trazodone, and bupropion
  • Do not use bupropion without comorbid depression.
• Other adjunct agents:
  • Because SSRI and SNRI can take several weeks to work, this is why you may consider giving the patients quick-acting adjunctive to help them while SSRI and SNRI start working.
  • These include gabapentin, pregabalin, hydroxyzine, and benzodiazepines.
• Some neat details on BZDs
  • Go with the lowest dose for the shortest duration possible because of tolerance.
  • If BZDs are used longer than 8 weeks, try to taper by no more 25% per week.
  • If BZDs are used longer than 1 year, try to taper by no more than 10% per week over 2-4 months.
  • Physiological Relief: Very effective short-term
  • Psychological Relief: Not very effective
• Buspirone
  • MoA: Partial 5-HT_1A agonist
  • Psychological Relief: Yes, but inconsistent and doesn’t help with comorbid depression
  • Dosing is TID because it has a short half-life. This is not a PRN medication.
  • Max dose: 60mg/day
  • Dizziness, nausea, HA
  • Interaction with 3A4 inhibitors, leading to increase serum buspirone level.
• Hydroxyzine
  • MoA: Antihistamine
  • It is fairly effective in a lot of cases.
  • If taken over a long period of time, the effects can be attenuated.
  • Quick onset (15-30 minutes) and dose 3-4 QD or PRN
  • Psychological Relief: Not at all
  • Physiological Relief: Yes
  • Side effects: think of anticholinergic effects
  • Like BZDs, caution in elderly, BPH, and narrow-angle glaucoma.
• Pregabalin
  • MoA: Reduce calcium influx by binding to the voltage-gated calcium
  • Psychological Relief: Yes
  • Physiological Relief: Yes
  • Take one week for onset
  • Dosing start with 150mg in 2-3 divided doses and titrate by 150-300mg once a week
  • ADR: Dizziness, sedation, dry mouth, ataxia, peripheral edema
• Propranolol
  • B1 and B2 antagonist
  • “Performance anxiety disorder”
  • Onset is 1-2 hours
  • Dosing is 10-20mg 30-60 minutes before anxiety inducing situation
  • ADR: Dizziness, hypotension, bronchospasm
• Quetiapine
  • MoA D2 and 5-HT2 antagonism
  • Onset is 1-3 weeks.
  • Start with 25 daily and hard max of 800mg per day.
  • ADR: weight gain, sedation, dry mouth, sexual dysfunction (SERT antagonism)

The KEY with SSRI/SNRI dosing is to start low and go slow. This is to reduce jitteriness and anxiety. The dose should be titrated to effect slowly. Patient should be educated to reduce early discontinuation.

SSRI/SNRI Dosing

1. Duloxetine – start with 30 or 60mg – titrate to 60-120mg per day
2. Escitalopram – start with 10mg – titrate to 10-20mg per day
3. Paroxetine – start with 20mg – titrate to 20-50mg per day
4. Sertraline – start with 50mg – titrate to 50-200mg per day
5. Venlafaxine XR – start with 37.5 or 75mg – titrate to 75-225mg per day
6. Vilazodone (Viibryd) – start with 10mg – titrate to 20-40mg per day
7. Vortioxetine (Trintellix) – start with 5mg – titrate to 5-20mg per day
8. Imipramine – start with 50 mg – titrate to 75-200mg per day

Special Populations:

• Pregnancy – caution but need to get under control
  • No paroxetine
  • No BZD
• Children and teens – behavioral therapy prefer
• Hepatic disease – Avoid duloxetine

How long to keep patients on therapy

After getting an adequate response, continue for at least 1 year before attempting to taper off.

SSRI –> SSRI + Adjunctive or increase dose –> Adjunctive alone

Panic Disorder

This is a spontaneous and intense fear followed by a change in behavior

Treatment:

First-line: SSRI or venlafaxine, short-term (4-6 week) benzodiazepines.

• SSRIs approved for PD are fluoxetine, paroxetine, and sertraline
• BZDs are usually dose with a regular schedule than PRN. Do not use as monotherapy in patients with depression
  • Prefer clonazepam (long action) and alprazolam (quick on and off)

Second-line: Other SSRI or imipramine

Adjunctive: Long-term BZDs or quetiapine (SGAs)

Social Anxiety Disorder

Fear of social situations

Treatment:

First-line: SSRI or venlafaxine

• SSRI approved for PD – paroxetine, sertraline, fluvoxamine, venlafaxine

Second-line: Other SSRI

Third-line: Augment with BZDs or gabapentin/pregabalin

Performance anxiety: propranolol