Anxiolytics Flashcards
What are the first-line agents (4) used for anxiety disorders?
Antidepressants such as SSRIs, duloxetine (Cymbalta), and Venlafaxine XR (Effexor XR)
Benzodiazepines
Buspirone (Buspar)
Hydroxyzine
What drugs are used to treat anxiety disorders?
Anxiolytics
What are the second line agents (2) used in the treatment of anxiety disorders?
Prazosin (Minipress)
Pregabalin (Lyrica)
What are the third line agents (4) that are used as alternative treatments for anxiety disorders that are primarily reserved for refractory cases due to concerns regarding safety and tolerability?
Antipsychotic agents– Minimal data supporting routine use; may be beneficial in refractory cases
Gabapentin (Neurontin)– Minimal data supporting its efficacy
Monoamine oxidase inhibitors
Tricyclic antidepressants
What is the mechanism of action for selective serotonin reuptake inhibitor’s?
They inhibit the reuptake of serotonin
What is the mechanism of action for duloxetine and venlafaxine?
They inhibit the reuptake of serotonin and norepinephrine
What is the mechanism of action for Buspirone?
It is a partial agonist at serotonin 1A receptors
What is the mechanism of action for hydroxyzine?
It is a histamine receptor antagonist
What is the mechanism of action of Prazosin?
It is an alpha-1 blocker primarily used in the treatment of hypertension
it may help nightmares and sleep disturbance in patients with PTSD
What is the mechanism of action of pregabalin?
It’s a calcium channel modulator inhibiting excitatory neurotransmitter release
It’s mechanism of action is very similar to gabapentin and structurally similar to GABA but does not act on benzodiazepine receptors
What are the 5 FDA approved indications for anxiolytic medications?
Generalized anxiety disorder
social phobia
panic disorder
posttraumatic stress disorder
obsessive-compulsive disorder
What is the non-FDA approved indication for prazosin?
It appears to be helpful for nightmares and sleep disturbance in patients with PTSD
What is the non-FDA approved indication for the use of pregabalin?
It has been largely studied in the treatment of general anxiety disorder
What is an adverse drug reaction more commonly observed with benzodiazepines such as diazepam, alprazolam and triazolam which have shorter half-lives, are used at higher doses, and are more lipophilic?
Anterograde amnesia – which is the short-term impairment of memory, and difficulty forming new memories
Can tolerance develop with long-term use of shorter half-life benzodiazepines such as diazepam, alprazolam, and triazolam?
Yes
Which adverse effect is associated with the use of duloxetine, hydroxyzine, and paroxetine?
Anti-cholinergic effects
What dose-related effect does duloxetine and venlafaxine XR exhibit?
Hypertension
What cardiovascular effect does prazosin exhibit?
Hypotension
What cardiovascular effect do the tricyclic antidepressants sometimes exhibit?
EKG changes, specifically QTC prolongation
Which class of medication can cause paradoxical excitation or disinhibition?
This may occur with benzodiazepines, especially among the very young and the very old; therefore, this may not be an ideal choice if patients are experiencing irritability, hostility and/or impulsivity
Benzodiazepines, duloxetine, hydroxyzine, paroxetine, and pregabalin share what side effect?
Sedation
Benzodiazepines with a longer half-life, for example flurazepam, may cause patients to experience what type of effect?
A “hangover” effect – prolonged CNS effects into the next day
Why should drugs that sedate be used cautiously in elderly patients?
If they have altered renal and/or hepatic function, this could result in elevated drug concentrations and an elevated fall risk
Which class of medications can have a stimulating effect?
Serotonergic antidepressant agents, especially the SSRIs
What are the 4 specific stimulating side effects seen with SSRI/serotonergic antidepressant agent use?
Insomnia, restlessness, agitation, and anxiety
Why is it important to “start low and go slow” when using pharmacological treatment for anxiety disorders?
In general, patients with anxiety disorders are more sensitive to medication side effects, therefore, one should consider starting at half the usual starting dose for depression, and titrate more slowly
As a result of the “start low and go slow” philosophy, what should a clinician expect over the course of treatment for patients with anxiety symptoms?
Due to the lower tolerability and slower titration schedule, full therapeutic benefits may be delayed. For example, it may take longer to see resolution of anxiety symptoms in comparison to depressive symptoms using the same agents
True or false: the effective dose of the medication being used to treat anxiety symptoms may end up being higher than that used for the treatment of depression.
True
Which 3 antidepressant agents are commonly associated with withdrawal symptoms? What is it due to? What specific symptoms (3) may be seen with missed doses or rapid tapers?
Venlafaxine XR, paroxetine and duloxetine
This is due to their short half-lives
Specifically, withdrawal symptoms may include insomnia, agitation, and anxiety with missed doses or rapid tapers
Generally speaking, what are the two options that will help minimize the withdrawal effects of antidepressant medications?
Resume the previous dose and taper more slowly; or
Switch to a different serotonergic antidepressant with a longer half-life, (eg. Fluoxetine) and continue to taper
Which type of benzodiazepines display withdrawal symptoms? What are three specific examples?
Agents with shorter half-lives
Lorazepam, alprazolam, or oxazepam
The withdrawal symptoms seen with benzodiazepines may mimic what type of disorders? Which specific symptoms (4) may be seen?
It may mimic anxiety disorders; specifically, rebounding anxiety, insomnia, agitation, and dysphoria may be seen
Which withdrawal symptom associated with benzodiazepine agents is most concerning?
Seizures
When tapering doses of benzodiazepines, which stage is better tolerated, the earlier stages or the final stages?
The earlier stages are better tolerated
Is there a specific time frame for tapering benzodiazepines?
No, there is no specific time frame, it should be largely based upon tolerability. However, a tapering schedule that is too long and drawn out (e.g., 6 months,) may also hinder a successful taper
Does a slow taper of benzodiazepines eliminate withdrawal effects?
No, it only minimizes withdrawal effects
When discontinuing benzodiazepines, what approach should be avoided?
Abrupt discontinuation
Depending on how long the patient was receiving the benzodiazepine, the dose, the half-life, tolerability, etc., how should outpatients be tapered?
Reduce the dose by approximately 10-20%/week or slower
What fact is important to remember when treating anxiety patients with serotonergic antidepressants?
Patients may mistake the stimulating effect of serotonergic antidepressants as a worsening of their illness, though these effects are often short-lived (lasting only days)
What’s the best way to help patients avoid stimulating effects of antidepressants and improve compliance?
Consider starting patients at a lower dose (in comparison to the starting dose for depression). Although the target dose may sometimes be higher than those used in the treatment of depression, slow titration is recommended to minimize these effects
To help patients avoid the stimulating effects of antidepressants and improve compliance, what other class of medications may be used during antidepressant initiation?
Benzodiazepines
What class of medications are often used to “bridge” patients who are starting an antidepressant? Why?
Benzodiazepines; because the therapeutic effects of antidepressants are usually delayed for several weeks
Benzodiazepines may be more effective than antidepressants for which specific anxiety disorder?
Social anxiety disorder
Benzodiazepines may worsen symptoms in which type of patients (2)?
Social anxiety disorder with comorbid depression
PTSD
Compare the onset of therapeutic activity between benzodiazepines vs. SSRI and SNRI antidepressants…
Benzodiazepines– Immediate
SSRI and SNRI antidepressants – delayed
Compare the risk of stimulating\anxiety-like side effects of benzodiazepines vs. SSRI and SNRI antidepressants….
Benzodiazepines – absent
SSRI and SNRI antidepressants– Can occur, especially with higher doses, rapid titrations and certain SSRIs (e.g., fluoxetine)
Compare the risk of dependence between benzodiazepines vs. SSRI and SNRI antidepressants…
Benzodiazepines – may occur, especially among patients with a history of substance abuse
SSRI and SNRI antidepressants– Absent
Compare the risk of withdrawal-related side effects for benzodiazepines vs. SSRI and SNRI antidepressants…
Benzodiazepines may occur, especially with longer use, agents with shorter half-lives, and with a rapid taper or abrupt discontinuation
SSRI and SNRI antidepressants– May occur with duloxetine, paroxetine, or Venlafaxine (Shorter half-lives)
Compare the risk of overdose with benzodiazepines vs. SSRI and SNRI antidepressants…
Benzodiazepines – it’s a risk, especially when taken with other CNS depressants, particularly alcohol
SSRI and SNRI antidepressants– Risk with tricyclic antidepressants: lethal QTC prolongation may occur
Compare the sedative side effects of benzodiazepines vs. SSRI and SNRI antidepressants….
Benzodiazepines – yes, although tolerance may develop
SSRI and SNRI antidepressants– Yes, particularly among agents with high antihistamine activity (e.g. Paroxetine) tolerance often develops
Compare the risk of cognitive impairment with benzodiazepines vs. SSRI and SNRI antidepressants….
Benzodiazepines – yes, especially with agents that are more lipophilic, with those with shorter half-lives, and at higher doses
SSRI and SNRI antidepressants– Possible with agents that have sedative and anti-cholinergic effects (e.g., paroxetine and duloxetine)
