Lecture 60 - Pharmacotherapy of Anxiety Disorders

Question 1

Drugs that can cause anxiety

Answer 1

albuterol, caffeine (high dose), decongestants, levothyroxine, steroids, stimulants (ADHD meds)

Question 2

Buspirone

Answer 2

Buspirone is a serotonin (5HT)-1a receptor agonist
approved for use in generalized anxiety disorder
should be dosed with a target of 10 mg - 15 mg three times daily (30-45 mg total/day)
May take up to 3 - 4 weeks for initial efficacy - patients should be counseled

Question 3

Benzodiazepines

Answer 3

Many treatment guidelines do not support the use of benzodiazepines in routine practice due to misuse potential, but the effect size for efficacy in anxiety disorders is higher than serotonergic antidepressants in some studies
Long-term use is not recommended - due to risk of dependence/tolerance
Acute withdrawal of benzodiazepines may lead to seizures that can be life-threatening
Warnings for the use of benzodiazepines with other CNS depressants and overdose death risk – specific warnings for co-prescribing with opioids

Question 4

Benzodiazepines cont.

Answer 4

Alprazolam, lorazepam, clonazepam, and oxazepam do not have an active metabolite and are less likely to accumulate, while they have a fall risk, not as high as for those with active metabolite
Diazepam, clorazepate, and chlordiazepoxide have a long-acting active metabolite (N-desmethyldiazepam) and may lead to hangover and fall risk, especially in the elderly
Discontinuation of benzodiazepines requires a slow taper over weeks to months
Beers criteria, may be inappropriate in the elderly; in elderly prefer LOT - lorazepam, oxazepam, temazepam

Question 5

Benzodiazepines SEs:

Answer 5

sedation, paradoxical excitement, swallowing difficulties, impairment of memory and recall, and psychomotor impairment

Question 6

Hydroxyzine

Answer 6

Hydroxyzine pamoate is FDA-approved for the
treatment of generalized anxiety disorder (can also use HCl salt for lower 10 mg dose)
It is most commonly used “as needed” for anxiety or insomnia instead of a benzodiazepine
Avoid use in the elderly due to anticholinergic side effects and fall risk

Question 7

Hydroxyzine SEs

Answer 7

Sedation and anticholinergic side
effects are prominent, QTc prolongation risk

Question 8

Propranolol

Answer 8

Decrease physiological symptoms of acute anxiety - tachycardia, sweating, flushing
for performance and situational anxiety
low doses - 10-20 mg 2-3 x a day
evaluate for history/current asthma and cardiovascular conditions

Question 9

Natural Products

Answer 9

Kava
St John’s Wort
Passionflower
Valerian
Chamomile

Question 10

Kava

Answer 10

may cause hepatotoxicity/liver failure use is not recommended; may cause platelet aggregation and aggravate symptoms of Parkinson’s disease

Question 11

St John’s Wort

Answer 11

commonly used for anxiety and depression; strong 3A4 inducer, watch for drug interactions

Question 12

Passionflower

Answer 12

may cause dizziness, ataxia, confusion, avoid in pregnancy due to a risk of uterine stimulation and induction of early labor

Question 13

Valerian

Answer 13

may have properties similar to benzodiazepines; avoid use of valerian in pregnancy; reports of hepatotoxicity

Question 14

Chamomile

Answer 14

(avoid with blood thinners and ragweed allergy), lavender (decrease B/P, constipation, headache, increased appetite), lemon balm (GI upset)

Question 15

Gabapentinoids and Quetiapine in Anxiety

Answer 15

Gabapentinoids may be considered in a patient with bipolar disorder who has anxiety symptoms or comorbid neuropathic pain
sleep medicine does not endorse the use of quetiapine for insomnia

Question 16

General Drug Therapy Principles for Anxiety Disorders

Answer 16

SSRIs and SNRIs are first-line therapy for all anxiety disorders
Buspirone can also be used first-line for generalized anxiety disorder
Benzodiazepines are FDA-approved to treat anxiety disorders, but treatment guidelines suggest using them only if necessary
* Atypical antipsychotics are not FDA-approved for anxiety disorders, but clinical evidence suggests efficacy for treatment-resistant OCD (aripiprazole and risperidone); may also be used for dissociative symptoms of PTSD

Question 17

DSM-5, TR Generalized Anxiety Disorder

Answer 17

Excessive anxiety/worry around a number of life events that is difficult to control, present for at least 6 months
Symptoms include at least 3 of the following:
* Restlessness/feeling keyed up or on edge
* Being easily fatigued
* Difficulty concentrating or mind “going blank”
* Irritability
* Muscle tension
* Sleep disturbances

Question 18

Treatment of GAD - Drugs

Answer 18

First-line maintenance treatment are the SSRI antidepressants
* Take 2 – 4 weeks for initial onset of sx relief
SNRI antidepressants may be useful: Useful first-line if patient also has a pain syndrome
Benzodiazepines: * “Bridge therapy” to cover time until onset of SSRI/SNRI, where appropriate
* MUST taper if the patient has been taking long-term treatment to avoid withdrawal
Buspirone: useful treatment if dosed high enough and pt is aware of how long it will take to work
Hydroxyzine may be useful as needed

Question 19

DSM-5, TR Social Anxiety Disorder

Answer 19

Persistent fear about social and/or performance situations in which the patient fears embarrassment or humiliation that is unreasonable
Specific situations may be avoided in a manner that interferes with the patient’s normal routine
Duration of symptoms is at least 6 months

Question 20

Treatment of Social Anxiety Disorder

Answer 20

SSRIs are 1st line treatment: paroxetine and sertraline are FDA approved
SNRIs may be useful if failure of SSRI: venlafaxine is FDA approved
Beta blockers may be useful for non-generalized performance related SAD

Question 21

DSM-5 and Panic Disorder

Answer 21

Recurrent, unexpected panic attacks: abrupt surge of intense fear or discomfort and is accompanied by at least 4 physical and psychological symptoms, including sweating, palpitations, nausea, dizziness, fear of losing control, “going crazy”, or dying
At least one attack has been followed by one month or more of at least one of the following: persistent concern about additional attacks or their consequences; Significant maladaptive change in behavior related to the attacks

Question 22

Treatment of Panic Disorder

Answer 22

SSRIs are first-line maintenance treatment – most are FDA- approved
SNRIs – Venlafaxine is FDA- approved, duloxetine is not, but has good clinical data
Benzodiazepines should not be considered first-line maintenance therapy unless there is inadequate response to serotonergic drugs:
Clonazepam and alprazolam are FDA-approved; Clinically, may see a benzodiazepine (usually alprazolam) used for panic attacks or for “bridge therapy” until onset of action of SSRIs if significant panic attacks are occurring

Question 23

DSM-5, TR Obesessive Compulsive Disorder

Answer 23

Obsessions: Recurrent thoughts or images that are intrusive and cause anxiety; patient attempts to ignore, suppress or neutralize with other thoughts or actions
Compulsions: Repetitive behaviors or mental acts performed in response to obsession; aimed at reducing or preventing distress; not always connected in a realistic way to the fear

Question 24

Treatment of OCD

Answer 24

The SSRIs are first-line treatment for OCD. Most are FDA-approved
A 25 – 50% reduction in symptoms can be expected.
If the patient fails a few trials of different SSRIs, clomipramine (TCA) is considered second-line treatment - more serotonergic TCA - used only for OCD
Antipsychotics are not FDA-approved for OCD,
may be considered as augmentation therapy
with SSRIs/SNRIs - risperidone has best clinical data for effectiveness; data available for haloperidol, aripiprazole, quetiapine, olanzapine

Question 25

DSM-5, TR Posttraumatic Stress Disorder

Answer 25

Exposure to real or threatened death, serious injury, or sexual violence (either victim, witness, discovery, exposure to details of traumatic event
flashbacks, reexperiencing, avoidance, hypervigilance
negative alterations in mood or cognition

Question 26

Treatment of PTSD

Answer 26

SSRIs/SNRIs are first-line treatment, only class of
drugs FDA-approved for PTSD
Prazosin may be helpful for sleep or nightmares
Benzodiazepines are NOT recommended in PTSD
Polytherapy is common in PTSD
Substance use is common
Cognitive behavioral therapy and eye movement desensitization and reprocessing may be helpful

Question 27

Selected Drug Therapy Issues in Anxiety Disorders

Answer 27

“Jitteriness” syndrome can result from the use of the SSRIs and SNRIs when treating anxiety disorders
* Initial doses should be lower than doses used for depression to minimize the “jitteriness” side effect
Onset of action for the SSRIs/SNRIs is 2 to 4 weeks, maximal response to a specific drug and dose may take 6 to 8 weeks
Evaluate the severity of impact on functionality by the anxiety disorder before considering using “bridge therapy” with benzodiazepines
* Abrupt d/c of benzodiazepines can be life-threatening

Question 28

Non-Pharmacologic Treatment of Anxiety Disorders

Answer 28

Psychotherapy and cognitive behavioral therapy
In PTSD – drug therapy may be more effective in civilian trauma (usually a one-time event) versus combat trauma (traumatic events occurring over a longer period of time), so non-drug treatments are especially useful