First line drugs
First line treatment for GAD FDA-approved
Duloxetine (Cymbalta), Escitalopram (Lexapro), Paroxetine (Paxil), Venlafaxine (Effexor), Alprazolam (Xanax)
Per lecture: SSRIs, SNRIs, benzodiazepines, buspirone, alpha 2 ligands (Pregabalin/Gabapentin)
SECOND line treatment for GAD
TCAs, Mirtazapine, Trazadone, SPARI (Stahls)
Receptors a1 and a2 review
a1 activation by NE: Turns ON SNS fight or flight
a2 activation by NE: TURNS OFF SNS
To REDUCE anxiety, you would want an
a1 antagonist AKA prazosin (Minipress) or
an a2 agonist clonidine (Catapres)
Gaba and anxiety +/-
- not enough GABA= anxiety
Fear/panic/phobia related brain locations
Amygdala circuit: locus coeruleus -> amygdala, noradrenergic (NE) involvement
Hippocampus Internal fearmonger) ->amygdala
NTs: 5HT, GABA Glutamate, NE, voltage gated ion channels
Benzos are ____ to GABA
Flumazenil is _____ to GABA
Benzos= agonist
Flumazenil= antagonist
First line treatment for Panic disorder/phobia treatment FDA-Approved
fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft) Alprazolam (Xanax), Clonazepam (Klonopin)
Per Lecture: SSRIs and SNRIs as well as benzodiazepines, and alpha2 ligands
SECOND line treatment for Panic disorder/phobia treatment and augmenting meds
TCAS, Mirtazapine and Trazodone, MAOIs
per lecture: Augmented w Buspirone (BuSpar), Alpha2 ligands (pregabalin and gabapentin)
Note from the book about OCD and SRIs
There is also some evidence that response to SRIs is slower in OCD than in depression; clinicians are therefore encouraged to prescribe an SRI for at least 12 weeks before deciding to switch agents or augment with another psychotropic.
Anxiety and Serotonin? +/-
-
Not enough serotonin may result in feeling anxious
per lecture part 2
Worry/obsession brain location
CSTC Pathway:
Cortico-striatal-thalamic- cortical pathway
NTs: DA(different than fear loop), 5HT, GABA, NE, glutamate, ion channels
Buspirone (Buspar) whats is its primary NT action, indication and areas of the brain it works in
5HT- partial agonist to pre and post-synaptic 5-HT1A receptors.
Anxiety, generally as an adjunct.
Enhances serotonin in the projection to the Amygdala, PFC and the thalamus
Social anxiety disorder first line
SSRI, SNRIs, and Alpha 2 ligands
Social anxiety second line
Beta blockers, benzos, MAOIs
how is the amount if NE related to anxiety
Can have too much OR too little and show signs of anxiety.
Per her lecture.
Bonus Depression + or - NE???
Depression/ NE/ -
What NT lives in the Locus coeruleus and where does it project to in the brain and what are its receptors it attacthes too.
what might you see with too much activity?
NE!!
LC to amygdalaattatches to a1 and b1
tremmor, panic attack, autonomic arousal: sweating and +HR, nightmares
Thanks dr. Stahl
What drug would be a good choice for the treatment of PTSD related nightmares? Why?
Prazosin (Minipress)
blocks alpha 1 adrenergic receotirs to reduce noradrenergic hyperactivation
OCD first line treatment FDA approved and from lecture
Clomipramine (Anafranil), Fluoxetine (Prozac), Fluvoxamine (Luvox), Paroxetine (Paxil), Sertraline (Zoloft)
Off Label – Citalopram (Celexa), Venlafaxine (Effexor), Vilazodone (Viibryd)
OCD second line and augmentation
TCAs, SNRIs or MAOI
several failed SSRI trials—consider high doses of SSRI or augmentation with an atypical antipsychotic
Augmentation of an SSRI w a Benzo, lithium, or buspirone
What drug would be a good choice for the treatment of PTSD and SAD? Why?
Clonidine (and maybe Guanfacine)
centrally acting alpha 2 agonists, lowers NE release in the Sympathetic nuclei of the brain, and resets the body's sympathetic tone to decrease arousal state
Also ADHD in 6-17 yr olds
PTSD first line FDA-approved
sertraline (Zoloft) and paroxetine (Paxil)
(Effexor & Fluoxetine are considered first line treatments in the VA/DoD Clinical Practice Guideline for PTSD)
PTSD second line
Buspirone (BuSpar), imipramine (Tofranil) and amitriptyline (Elavil), MAOIs & Alpha 2 ligands (per Stahl)
Caution with Benzos
adjunctive: naltrexone, mirtazapine, acamprosate, beta blickers alapha1 antagoist.