PHRM845 Exam 4 (Ott)

Question 1

Epidemiology of anxiety disorders

Answer 1

-All of us experience anxiety
-Most commonly occurring psychiatric
disorders
-Usually develop before the age of 30 (just like all mental health disorders, there is age equality)
-More commonly diagnosed in women (may be because women seek tx more)
-1-year prevalence rate = ~ 20% in adults
-Anxiety is a normal and beneficial response to
situations that are perceived as threatening,
frightening, or disturbing
-Normal anxiety becomes a disorder when it
significantly impacts physical, occupational,
and/or social functioning

Question 2

GAD

Answer 2

Revved up and always feeling anxious
*anxiety is a co-morbid condition (offer tx for it)
*impeding sense of doom
*Feel dizzy/out of sorts

Question 3

Drugs that can cause anxiety

Answer 3

• Albuterol
• Antipsychotics
• Bupropion
• Caffeine (high dose-800 mg/day=half a pot)
• Decongestants (Sudafed)
• Cocaine, methamphetamine
• Levothyroxine (hyperthyroid=jittery and amped up)
• Steroids
• Stimulants (ADHD meds)
• Theophylline

Question 4

Medication classes for anxiety

Answer 4

Buspirone-5HT; partial agonist; only for GAD
Benzodiazepines
SSRIs
SNRIs
Hydroxyzine-serotonergic properties
Herbal Supplements

Question 5

What anxiety medication is more effective than all the others?

Answer 5

Benzodiazepines

Question 6

Buspirone

Answer 6

-Buspirone is a serotonin (5HT)-1a receptor partial agonist
-Approved for use in generalized anxiety disorder
-Generally viewed with skepticism regarding efficacy by both patients and providers
Often not dosed appropriately for efficacy
* Should be dosed with a target of 10 mg – 15 mg three times daily (30 mg – 45 mg total/day)
**Some MD ramp up too quick or don’t wait long enough for effect
* 3A4 substrate – watch for interactions with 3A4 inducers and inhibitors
May take up to 3 - 4 weeks for initial efficacy - patients should be counseled
Patients who have taken benzodiazepines before may not be receptive to long onset of action of buspirone
**NOT very effective PRN

Question 7

Benzodiazepines

Answer 7

• Most commonly used benzodiazepines include alprazolam,
  lorazepam, clonazepam, and diazepam - CIV controlled
  substances - misuse potential
• 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
• Often prescribed PRN or not dosed appropriately in routine
  doses to cover anxiety symptoms
• Long-term use is not recommended due to risk of
  dependence/tolerance; withdrawal symptoms can occur in
  patients who take benzodiazepines for as little as a few months
• 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 8

Describe the effect size of BZD

Answer 8

Average effect size is 0.4, but benzos effect size is 0.5 which means it is very effective for more people.

Question 9

Impact of abruptly stopping benzo

Answer 9

Abruptly stopping benzos or alcohol results in a high risk of death.
-Call physician if patient runs out rather than absolute refusal

Question 10

Designer benzos

Answer 10

Increase the risk of fatality and are more dangerous than prescribed benzos

Question 11

Metabolism of benzos

Answer 11

Onset of anxiolytic effect is dependent on rate of absorption and distribution into CNS
* Alprazolam, lorazepam, clonazepam, and oxazepam do not have an active metabolite and are less likely to accumulate, while they have a fall risk, it is not as high
as for those with an 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 (half-life is about 100 hours which is dangerous).

Question 12

Discontinuation of benzos

Answer 12

Discontinuation of benzodiazepines requires a slow taper over weeks to months depending on how long the patient has been taking the benzodiazepine and how they tolerate dose decreases (if taking for 6 months, taper for 6 mos-1 year)

Question 13

SE of benzos

Answer 13

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

Question 14

Benzos in elderly

Answer 14

• Beer’s Criteria: may be inappropriate in the elderly
  –confusion, dizziness, falls; risk of paradoxical reaction (hyperactivity, agitation, aggression)–>bouncing around because it gives a lot of people energy
• In elderly – prefer L-O-T (lorazepam, oxazepam, temazepam) –>these do NOT have active metabolites so it is good for ppl with fall risk

Question 15

Hydroxyzine

Answer 15

-Has serotonergic effect when taken routinely
-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, especially for patients with a history of substance use
-Serotonin 5HT2A antagonist and histamine
H1 receptor antagonist
-Sedation and anticholinergic side effects are prominent,
-QTc prolongation risk
-Avoid use in the elderly due to anticholinergic
side effects and fall risk (can dry things out and cause excessive sedation)

Question 16

Propranolol

Answer 16

-Decrease physiological symptoms of acute
anxiety
* Tachycardia, sweating, flushing
-Useful for performance and situational anxiety in as needed doses
-Low doses – 10 mg – 20 mg two – three times
daily or LA dosage form
-Evaluate for history/current asthma and
cardiovascular conditions
-May mask hyperglycemia and exacerbate
depression symptoms
**Beneficial for stage fright
**Targets physiological sx (sweating and increased heart rate) to decrease anxiety

Question 17

Kava

Answer 17

• Kava may cause hepatotoxicity/liver failure use is not recommended; may cause platelet
  aggregation and aggravate symptoms of Parkinson’s disease
  *Interacts with benzo receptor

Question 18

St. John’s Wort

Answer 18

St John’s Wort – commonly used for anxiety and depression; strong 3A4 inducer, watch for drug interactions
*May increase serotonin syndrome
*Decreases effectiveness of antipsychotic

Question 19

Passionflower

Answer 19

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

Question 20

Valerian

Answer 20

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

Question 21

Chamomile

Answer 21

Chamomile (avoid with blood thinners and
ragweed allergy), lavender (decrease B/P,
constipation, headache, increased appetite),
lemon balm (GI upset)
*Possible cross-allergic reaction if allergic to ragweed/pollen

Question 22

Gabapentinoids and quetiapine in anxiety

Answer 22

-Gabapentin and pregabalin are occasionally prescribed for generalized anxiety disorder; there is a limited evidence base
and no FDA-approval (interacts with GABA receptor like Benzos do)
-Gabapentinoids may be considered in a patient with bipolar disorder who has anxiety symptoms or comorbid neuropathic pain
-The active metabolite of quetiapine (norquetiapine) is theorized to have anxiolytic properties; quetiapine is sometimes prescribed both for anxiety and sleep; the
evidence base is limited for anxiety and sleep medicine does not endorse the use of quetiapine for insomnia

Question 23

What are gabapentinoids used for?

Answer 23

Neuropathic pain and anxiety

Question 24

What CYP substrate is quetiapine?

Answer 24

3A4

Question 25

General drug therapy principles for anxiety disorders

Answer 25

• SSRIs and SNRIs (reference the depression lecture slides for specific drug information) are first-line therapy for all anxiety disorders
• Buspirone can also be used first-line for generalized anxiety disorder (or adjunct for panic 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
• Herbal therapies, such as kava and valerian, may be used, but have side effects and drug interactions - important to ask patients if they are using these supplements

Question 26

DSM-5, TR GAD definition and symptoms

Answer 26

Excessive anxiety/worry around a
number of life events that is difficult to
control, present for at least 6 months (try to get past coping skills)
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
* Cognitive behavioral therapy
**Hard to target what exactly anxiety is caused by

Question 27

Treating GAD

Answer 27

**All meds are equally effective
-First-line maintenance treatment
are the SSRI antidepressants
* Take 2 – 4 weeks for initial onset of symptom relief (give with PRN med such as BZD)
* Paroxetine and escitalopram are FDA approved
-SNRI antidepressants may be
useful
* Similar timeframe for onset of action
* Duloxetine and venlafaxine are FDA-approved
* Useful first-line if patient also has a pain
syndrome
-Benzodiazepines
* Used to be commonly prescribed, concern for
misuse
* “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
*With serotonergic meds, it makes pts jittery in the first couple of days, but goes away
-Buspirone
* Useful treatment if dosed high enough and
patient is aware of how long it will take to
work
-Hydroxyzine may be useful as
needed to treat symptoms of
anxiety; monitor for anticholinergic
side effects and QTc prolongation
risk

Question 28

DSM-5, TR Social Anxiety Disorder

Answer 28

-Persistent fear about social and/or performance situations in which the patient fears embarrassment or humiliation that is unreasonable
-Fear of being scrutinized by unfamiliar people
-Specific situations may be avoided in a manner that interferes with the patient’s normal routine
-If situation is endured, it is with stress
Duration of symptoms is at least 6 months
**A lot of the time, these pts will stop going out

Question 29

Treatment of Social Anxiety Disorder

Answer 29

-SSRIs are firstline 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 nongeneralized, performancerelated SAD
-Mirtazapine, benzodiazepines, and anticonvulsants have limited clinical data – not
FDA-approved
-Phenelzine is reserved for
treatment-resistant SAD, (must be
monotherapy, not FDA-approved)

Question 30

DSM-5 Panic Disorder definition

Answer 30

-All you have to do is anticipate it
-1st time is unprovoked and unexpected
-Recurrent, unexpected panic attacks
* Panic attack is an abrupt surge of intense fear or discomfort that reaches a peak in minutes and is accompanied by at least 4 physical and psychological symptoms, including sweating,
palpitations, nausea, dizziness, fear of losing control, “going crazy”, or dying (brain thinks they are not going to make it)
-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
-May lead to agoraphobia, which is a separate
diagnosis
**Negative behaviors can start to impact a person’s life

Question 31

Treatment of panic disorder

Answer 31

-SSRIs are first-line maintenance treatment – most are FDA-approved
-SNRIs – Venlafaxine is FDA-approved, duloxetine is not, but has good clinical data
-TCAs, mirtazapine, MAO inhibitors – not FDA-approved, have shown similar efficacy to
SSRIs, but tolerability limits usefulness for TCAs and MAOIs
-Benzodiazepines should not be
considered first-line maintenance therapy unless there is inadequate response to
serotonergic drug (clonazepam and alprazolam are FDA-approved)

Question 32

DSM-5, TR Obsessive-compulsive disorder (OCD)

Answer 32

-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
-Must be present and recognized as excessive or unreasonable
-Must cause marked distress and take more than 1 hour per day OR interfere significantly with functioning
-Content of obsessions/compulsions is not restricted to another psychiatric disorder
*ex: if I don’t do ___, something bad is going to happen
**Germ phobia

Question 33

Treatment of OCD

Answer 33

-The SSRIs are first-line treatment for OCD. (Most are FDA-approved)
-A 25 – 50% reduction in symptoms can be
expected. (pt needs to know expectation!)
-If the patient fails a few trials of different SSRIs, clomipramine (TCA) is considered second-line treatment (More serotonergic TCA – only used for OCD)
-Venlafaxine XR has been studied with effectiveness in clinical trials similar to
SSRIs
-Antipsychotics are not FDA-approved for OCD,
may be considered as augmentation therapy
with SSRIs/SNRI (low doses of these meds)
* Risperidone has the best clinical data for effectiveness
* Data is available for haloperidol, aripiprazole,
quetiapine, and olanzapine, may be inconsistent efficacy

Question 34

DSM-5, TR Posttraumatic stress disorder (PTSD)

Answer 34

-Exposure to real or threatened death, serious injury, or sexual violence (either victim, witness, discovery, exposure to details of traumatic event
-Involuntary, recurrent, distressing memories or dreams; dissociative reactions (flashbacks), intense/prolonged distress (reexperiencing)
-Avoidance of stimuli associated with the event; efforts to avoid external reminders (avoidance)
-Marked alterations in reactivity or arousal; exaggerated startle response; sleep disturbance (hypervigilance)–constantly looking around
-Negative alterations in mood or cognition; inability to recall parts of the event; decreased interest in activities; estrangement
*4 main things of PTSD: flashbacks, reexperiencing, avoidance, hypervigilance

Question 35

Treatment of PTSD

Answer 35

-SSRIs/SNRIs are first-line treatment, only class of drugs FDA-approved for PTSD
-With multiple failed trials of the above, can consider mirtazapine
-Prazosin may be helpful for sleep or nightmares, although recent evidence suggests less effectiveness (has been removed from the
VA PTSD treatment guidelines; topiramate has also been studied
-Benzodiazepines are NOT recommended in PTSD; no evidence of reduction in core
symptoms; may potentiate fear response and worsen recovery from trauma
-Polytherapy is common in PTSD, attempts to target specific symptoms – watch
for additive side effects and drug interactions
-Substance use is common in PTSD – should try to treat both disorders simultaneously
-Cognitive behavioral therapy and eye movement desensitization and reprocessing may be helpful (exposure tx: put in elevator if scared of them)

Question 36

Theoretically, what causes PTSD?

Answer 36

a large burst of norepinephrine
through the amygdala, where some memories are stored.

Question 37

Selected drug therapy issues in anxiety disorders

Answer 37

• “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; need to ensure appropriate follow-up so that the dose can be increased when needed
• Example: citalopram 10mg daily instead of citalopram 20mg daily
• Counsel about onset of action and antidepressant withdrawal syndrome
• 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 38

Non-pharmacological treatment of anxiety disorders

Answer 38

-Psychotherapy and cognitive behavioral therapy are mainstays of treatment for anxiety disorders
-Drug therapy often helps to improve the effectiveness of these treatment modalities
-The lack of availability of trained providers and limited insurance coverage of cognitive behavioral therapy is often a barrier to this
type of treatment
-Anxiety disorders are commonly diagnosed after a long-standing period of illness
-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