S54 - Pharmacology of Anxiety Disorders Flashcards
_____________ are the most effective and safe (relatively) for rapid relief of anxiety symptoms.
Benzodiazepines
BZD's clobazam (Onfi®) clonazepam (Klonopin®) clorazepate (Tranxene®) diazepam (Valium®) lorazepam (Ativan®)
_________ is an optional treatment in patients without comorbid depression or other anxiety disorders.
Buspirone (Buspar)
First Line therapy for Generalized Anxiethy Disorder (GAD)
Duloxetine (Cymbalta) Escitalopram (Lexapro) Paroxetine (Paxil) Sertraline (Zoloft) Venlafexine XR (Effexor)
First Line therapy for Panic Disorder
SSRI’s
- fluoxetine (Prozac)
- sertraline (Zoloft)
- paroxetine (Paxil)
- citalopram (Celexa)
- escitalopram (Lexapro)
- vortioxetine (Trintellix)
Venlafexine XR (Effexor)
First Line Therapy for Social Anxiety Disorder
Escitalopram (Lexapro) Paroxetine (Paxil) Sertraline (Zoloft) Venlafexine XR (Effexor) Fluvoxemine CR
Aytpical antipsychotics low-dose have been used for GAD –
Quetiapine 150 mg = paroxetine 20 mg/day.
Pregabalin is used in Europe as a first-line agent for GAD.
Off-label at best in the USA.
Not included into treatment algorithms.
Antidepressants are considered the first-line agents in GAD.
Duloxetine (Cymbalta) Escitalopram (Lexapro) Paroxetine (Paxil) Sertraline (Zoloft) Venlafexine XR (Effexor)
FDA approved for Generalized Anxiety Disorder (GAD)
Response is delayed 2-4 weeks.
paroxetine (Paxil)
duloxetine (Cymbalta)
venlafaxine (Effexor)
escitalopram (Lexapro)
________ is FDA approved for PD with or without agoraphobia.
Alprazolam (Xanax)
FDA Approved agents for acute anxiety
Alprazolam (Xanax) clonazepam (Klonopin®) clorazepate (Tranxene®) diazepam (Valium®) lorazepam (Ativan®) chlordiazepoxide (Librium) Oxazepam (Serax)
IM administration of diazepam and chlordiazepoxide should be AVOIDED –
erratic absorption and painful.
Which BZD’s are glucuronidated?
Only lorazepam and oxazepam are glucuronidated
Clonazepam undergoes
nitroreduction.
Diazepam is also metabolized by
CYP 2C19
__________ is a prodrug converted to DMDZ in the GI tract under acidic pH. Watch out for antacid use!
Clorazepate
Long-acting BZ are metabolized to desmethyldiazepam (DMDZ) – active metabolite.
BZ efficacy – 65-75% response rate within 2 weeks.
Only effective for the
somatic symptoms.
Unique to benzodiazepines where patient can become highly agitated and increased BZD’s increases agitation.
Disinhibition syndrome
_________ _________ – rebound anxiety with Increased symptoms greater than baseline.
Benzodiazepine discontinuation
BZD’s have drug interactions with:
CYP3A4 inhibitors (ketoconazole) and inducers (carbamazepine).
__________ – nonBZ without anticonvulsant, hypnotic, motor impairment or dependence .
Buspirone (Buspar)
2nd line agent for GAD.
Delayed onset > 2 weeks.
MOA: 5-HT1A partial agonist activity at presymaptic neurons ↓ firing of 5-HT neurons.
Do not use with MAOI’s for concern of serotonin syndrome.
Pregnancy avoids
Antidepressants (SSRI’s and TCA’s) are preferred agents for pregnant pts. except paroxetine.
Benzodiazepines (BZs) associated with cleft lip and cleft palate in babies.
Clinicians avoid BZs during the 1st trimester.
BZs use in the 3rd trimester: sedation, withdrawal and “floppy baby syndrome.”
Alprazolam and lorazepam reported to cause neonatal withdrawal symptoms.
Panic Disorder (PND)
SSRI’s are considered first-line due to safety and tolerability.
Combination of psychotherapy and drug therapy.
CBT is used 16-20 hrs over 4 months
Panic Disorder (PND) treatment duration
Acute phase TX. : 1-3 months, therapy altered if no response found 6-8 weeks.
Maintenance Tx. : 12-24 months, drug dc’d over 4-6 months.
Monitor for various issues – BZ dependence, SSRI withdrawal syndrome and etc
FDA Approved for Generalized Anxiety Disorder
Sertraline (Zoloft) Paroxetine (Paxil) Escitalopram (Lexapro) Venlafaxine (Effexor) Duloxetine (Cymbalta) Buspirone (Buspar)
FDA Approved for Social Anxiety Disorder
Sertraline (Zoloft)
Paroxetine (Paxil)
Fluvoxamine
Venlafaxine (Effexor)
FDA Approved for Panic Disorder
Sertraline (Zoloft)
Paroxetine (Paxil)
Clonazepam (Klonopin)
Alprazolam (Xanax)
Special populations: SAD present in young children.
Monitored closely for suicidal ideation when SSRI or SNRI is used.
BZs’ last line of agents for children with SAD.
1/5 pts. also have alcohol use.
Do not use MOAI’s.
Careful use of BZs.
SNRI’s: effective for pts. Who do not respond to SSRI’s.
Use like for depressed pts.
Mirtazapine 30 mg/day was used in women over 10 weeks.
BZ’s: reserve use for pts. who can not use SNRI’s or SSRI’s.
Gabapentin was reported to be effective.
beta-blockers were found not be effective for daily use.
__________ were developed for treatment of anxiety disorders, but are 2nd line agents after SSRIs/SNRIs
Benzodiazepines
Are the benzodiazepines considered the “first-line” agent for GAD treatment?
NO… SSRIs/SNRIs
Can benzodiazepines be abruptly discontinued?
NO… withdrawal symptoms can occur
What is the minimum amount of time needed for treatment with a SSRI for patient with PND who responses to a SSRI agent?
Minimum 12 mons/ can be up to 24 mos.
BZ’s: alprazolam is the ideal agent who need rapid relief (1-2 weeks). Relapse rates 50% or higher.
True
SNRI’s was reported to be effective 54-60% respond.
True
SAD: When drug were dc’d after 2-3 months, relapse > than 5-12 months.
True
SSRI’s and SNRI’s are equally effective.
TCA’s are not effective in SAD.
True
SAD Start with: - fluoxetine (Prozac) - sertraline (Zoloft) - paroxetine (Paxil) - citalopram (Celexa) - escitalopram (Lexapro) - vortioxetine (Trintellix) or venlafexine for 12 weeks
True
SAD Start with: - fluoxetine (Prozac) - sertraline (Zoloft) - paroxetine (Paxil) - citalopram (Celexa) - escitalopram (Lexapro) - vortioxetine (Trintellix) or venlafexine for 12 weeks
IF RESPONSE
Continue for 12 weeks
SAD Start with: - fluoxetine (Prozac) - sertraline (Zoloft) - paroxetine (Paxil) - citalopram (Celexa) - escitalopram (Lexapro) - vortioxetine (Trintellix) or venlafexine for 12 weeks
IF NO RESPONSE
SWITCH SSRI or if not used venlafexine use that
SAD Start with: - fluoxetine (Prozac) - sertraline (Zoloft) - paroxetine (Paxil) - citalopram (Celexa) - escitalopram (Lexapro) - vortioxetine (Trintellix) or venlafexine for 12 weeks
if PARTIAL response
Augment with Buspar or clonazepam
SNRI’s: effective for pts. Who do not respond to SSRI’s
True
Mirtazapine 30 mg/day was used in women over 10 weeks.
True