Anxiety ~ Peters

2nd Gen SSRI MOA

inhibition of presynaptic serotonin reuptake → increased serotonin in the synaptic cleft

blocking SERT

SSRI Dosing Overall

once daily except [fluvoxamine]

dosed at bedtime or morning depending on tolerability

SSRI: Fluoxetine [Prozac] ~ Clinical Pearl

Most Activating SSRI ~ take in morning bc will cause insomnia at night

Long-Acting: t1/2 up to 6d [in chronic use] ~ better for pt who forgets to take meds

SSRI: Paroxetine [Paxil] AE

Crazy Sedation!!
many AE: antichol [dry], weight gain, sexual dysfunction, tremor

SSRI: Paroxetine [Paxil] Clinical Pearl

incr withdrawal effects w/ missed doses [shorter t1/2]

SSRI: Sertraline [Zoloft] AE

complaints of GI initially

SSRI: Sertraline [Zoloft] ContraIndication

no use in severe liver impairment

SSRI: Citalopram [Celexa] Dosing

Initial = 10mg daily

Maintenance = 20mg daily

Max = 40mg daily

• dose over 40 not recommended due to prolonged QTc/TdP risk

SSRI: Citalopram [Celexa] Special Populations

not for the elderly or patients w/ hepatic impairment

SSRI: Escitalopram [Lexapro]

Initial: 10mg QD

Max: 20mg QD

well tolerated & minimal DDI

SSRI: Fluvoxamine [Luvox] AE

most sedation over any antidepressant

SSRI: Fluvoxamine [Luvox] Dosing

Initial = 50mg at bedtime

Increase by 50mg weekly; max dose = 300mg/day

TDD > 100mg should be given BID

Given ONCE A WEEK VS QD

SSRI: Fluvoxamine [Lovox] Clinical Pearl

Approved for: Obsessive Compulsive Disorder [OCD]

off-label ~ depression

SNRI: MOA

maintain activity at 5-HT recep while adding NE reuptake inhibition

SNRI Overall

Worse Discontinuation Syndrome than SSRI

Less Sedating compared to SSRI

SNRI: Venlafaxine [Effexor] Dosing

ER Preferred

75mg PO QD??

Target Dose: 150mg/d - 225

SNRI: Venlafaxine [Effexor] Caution

pt with HTN

dose related [BP incr ~ >225mg/d]

OK to use in HTN if controlled

SNRI: Venlafaxine [Effexor] Clinical Pearl

dose reduction in renal impairment

SNRI: Duloxetine [Cymbalta] Use

indicated for various pain syndromes [neuropathy]

SNRI: Duloxetine [Cymbalta] ContraIndicated

in closed angle glaucoma

SNRI: Duloxetine [Cymbalta] Avoid

in renal impairment [CrCl <30]

+ hepatic dysfunction

SNRI: Duloxetine [Cymbalta] AE

more antichol than venlafaxine [dry mouth, constipation, blur vision]

SNRI: Desvenlafaxine [Pristiq] AE

Hypotension

SNRI: Levomilnacipran [Fetzima] AE

hypotension & nausea is guranteed almost

SNRI: Levomilnacipran [Fetzima] Clinical Pearl

dose reduction in renal impairment [CrCl < 60]

Non-Organic Causes of Anxiety

Bronchodilators

Stimulants

Corticosteroids

Levothyroxine

SSRI Anxiety Dosing Guidleines

starting dose can be ½ of depression

may cause overstimulation→ incr anxiety when starting

anxiolytic effects seen in 2-4 weeks

Bupropion [Wellbutrin] MOA

DA + NE reuptake inhibitor

Bupropion [Wellbutrin] IR Dosing!!!

100mg BID [max 450mg in 3-4 doses]

Bupropion [Wellbutrin] SR Dosing

150mg BID [max 400mg in 2 doses {BID}]

Bupropion [Wellbutrin] ER/XL Dosing

150mg QD, max 450mg QD

Bupropion [Wellbutrin] Clinical Pearl

Very Activating:

avoid 2nd dose of SR after 2pm

avoid in uncontrolled anxiety

Bupropion [Wellbutrin] Indications

vegetative symptoms/melancholic syndrome

• sleep in bed all day & night, super unthusiaticate

sexual dysfunction or weight gain from SSRI

Bupropion [Wellbutrin] Contraindications

in patients with history of seizures

• don’t use in pt in withdrawal from alc or BZD

in patients with eating disorders

Mirtazapine [Remeron] MOA

central alpha-2 antag → incr NE & serotonin

antag at Histamine, 5-HT2, 5-HT3, alpha-1 recep

Mirtazapine [Remeron] Dose SE

low dose: sedation & weight gain

high dose: loss of sedation + appetite stimulation

Mirtazapine [Remeron] Indications

for concomitant insomnia & malnourished patients

Vortioxetine [Trintellix] MOA

SSRI plus

• 5HT3 and 5HT1D antag

• 5HT1A ag

• 5HT1B partial ag

Vilazodone [Viibyrd] Clinical Pearls

less potent serotonin reuptake = less sexual dysfunction

take with food

Vilazodone [Viibyrd] MOA

SSRI + 5HT1a partial ag

Buspirone [Buspar] MOA

partial agonist of 5HT1a

± agonist of dopamine receptors

purely anxiolytic

Buspirone [Buspar] Dosing

10-15mg BID-TID [max dose 60mg/d]

best if scheduled

best if dosed at least BID

Buspirone [Buspar] Common AE

dizziness, drowsiness, nausea

Benzodiazepines [BZD] MOA

GABA agonists

BZD Use

panic disorder

severely distressing situation [flight, MRI]

severe anxiety symptoms when starting antidepressants

treatment refractory cases [scheduled doses, longer-acting agents]

BZD SE

sedation

hypotension

respiratory depression

cognitive/motor impairments [freeze dried tequila]

BZD Preferred Meds in Hepatic Dysfunction

Lorazepam, Temazepam, Oxazepam

BZD Withdrawal Symptoms

incr anxiety

tremors

tachycardia

hallucinations

seizures

*withdrawal seen after dailuse for >4 weeks

BZDs: Long Acting Agents

Clonazepam, Diazepam

used for consolidation method [switch to __ agent then taper every 3-7days]

Anticonvulsants [Pregabalin & Gabapentin] Overall

off-label use: anxiety

may be used as monotherapy or in addition to antidepressants

both agents reduced in renal dysfunction [CrCl <60mL/min]

Pregabalin [Lyrica] MOA

decr several neurotransmitters [NE, Dopamine, Serotonin, Glutamate] transmission through decr Ca release at nerve terminals

Pregabalin [Lyrica] Dosing + Overall

dose: 150-600mg QD divided either BID or TID

may see symptom reduction by day 7

may improve pt with significant sleep disturbances

Pregabalin & Gabapentin SE

HA, sedation, dizziness, fatigue

Gabapentin [Neurontin] MOA

decr several neurotransmitters [NE, Dopamine, Serotonin, Glutamate] transmission through decr Ca release at nerve terminals ~~ less potent receptor binding

Gabapentin [Neurontin] Dosing + Overall

initial: 300mg BID-TID

max: 3600mg QD either TID or QID

concern for misuse exists

Antihistamine [Hydroxyzine] MOA + Dosing

25-50mg prn up to QID

mostly sedating but can have some calming effects [glorified benadryl]

Antihistamine [Hydroxyzine] SE

antichol, blurred, vision, confusion, orthostatic hypotension

Antipsychotics

none have FDA approval + none are monotherapy

2nd Gen [atypical] agents studied/ used

Beta Blockers [Propranolol] Dosing + Overall

5-10mg TID [scheduled preferred]

helpful with autonomic symptoms of anxiety [tremor, tachycardia]

used for performance anxiety [public speaking]

** not gonna help with panic, but lower HR to relieve more anxiety

GAD Overall

“worry warts”

anxiety caused by everyday occurrence [ job, family, finances]

GAD Treatment

psychotherapy [CBT]

1st line: SSRI/SNRI [FDA approved: lexapro, zoloft, paxil, effexor, xymbalta]

1B line: anticonvulsant [pregab]

2nd line: BZD

Add Ons: TCA [imipramine] reserved due to SE, Buproprion [effective if anxiety not worsened], vilazodone/vortioxetine [have FDA approval for GAD], Quetiapine ER [approved for GAD but have high dropout rates], Buspirone [not as effective as antidepressants as monotx]

GAD Follow-Up/Monitoring

GAD-7 Score >8 = GAD diagnosis

HAM-A Score <7 = GAD Goal

Panic Disorder Overall

recurrent, unexpected panic attacks + 1 mo of persistent worry about future attacks

Panic Disorder Treatment

CBT »»» Meds

1st line: SSRI/ SNRI

• start with low doses + titrate slowly up

• may use BZD during 1st weeks of titration

2nd line: TCA [not as well tolerated], Mirtazapine [as effective as fluoxetine], BZD [use PRN like pill-in-pocket]

3rd line: MAOI [ poor tolerability], atypical antipsychotics [add-on in resistant cases], gabapentin [adjunt in severely ill pt]

Panic Disorder Follow-Up/Monitoring

Goal <1 on each item on sheehan disability scale

PTSD Overall

exposure, intrusion, avoidance, alter in mood & cognition, alter arousal & reactivity

PTSD Treatment

psychotherapy »»» meds

1st line: SSRI/ SNRI [prozac, paxil, zoloft, effexor]

• effexor & prozac preferred in military/combat related PTSD

2nd Line: mirtazapine [help w/ sleep or nightmares], prazosin [specifically used for sleep/nightmare & dose limit SE of hypotension,dizzy,syncope], Trazodone [sleep/nightmares]

Add-On: anticonvulsants: depakote, LMTG, CBMZP [± benefits for irritability related to hyperarousal], antipsychotics: aripip, risp, quet [help intrusive thoughts]

Last-Line: Do not use BZD

OCD Overall

recurrent, persistent & intrusive thoughts that cause anxiety

actions pt feel compelled to perform to decr obsession-induced anxiety

significant imapct quality of life [>1h/d spent on OCD]

OCD Treatment

CBT > meds

1st line: SSRI [higher doses than depression]

2nd line: SNRI, TCA clomipramine [only time TCA useful]

3rd line: antipsychotics [help obsessions], anticonvulsants [help with both parts]

Last Line: BZD