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Depression Pharma

Behavioral Medicine Pharmacology

SSRI MOA Selectively inhibit 5-HT reuptake by blocking 5-HT transporter
SSRI: Most potent SSRIs re: blocking 5-HT transporter paroxetine & citalopram
SSRIs that produce effect on NE: Fluoxetine and paroxetine (doses > 40mg)
SSRIs: Advantages Low affinity for histamine- 1, alpha-1, muscarinic (M) rec; so low sedation, no orthostasis, dry mouth or CV issues
SSRI w/longest half life fluoxetine
Most common AE reason for SSRI early DC GI problems (titrate slowly, take w/meals)
most common SSRI AE when starting drug Akathisia (esp w/fluoxetine)
Tx for SSRI akathisia Start low, early AM, benzo, trazo, propanolol
Sexual dysfn greatest/least with: greatest: paroxetine; least: citalopram
SSRI AE: sedation greatest with: paroxetine (d/t anticholinergic properties)
Serotonin syndrome S/S Hyperreflexia, tremor, GI complaints, CV problems, seizures, respiratory depression, coma, death; concern re: SSRI combo w/other drugs
SSRI withdrawal S/S Nightmares, flu-like symptoms, GI, shock-like sensations, & insomnia (seen usually in 2 to 7 days after abrupt d/c)
SSRI withdrawal worst with: paroxetine & sertraline (switch to fluox?)
SSRI benefit seen in: atypical, psychotic, and dysthymia
Fluoxetine effective dose range 20-40 mg/day
Wt gain: SSRIs with greatest/least Least: fluox; greatest: paroxetine
Paroxetine effective dose range 30-50 mg/day
Citalopram/escitalopram effective dose range 20-60 mg/day
Lexapro effective dose range 10-20mg/day
Classes: equal in depression tx SSRI, SNRI, atypicals
SNRI MOA Block reuptake of 5-HT and NE (& DA)
SNRI MOA: Venlafaxine only produces effects on NE at: a higher dose (so push dose pretty high)
SNRI MOA: Duloxetine has a high level of effect on: both 5-HT and NE
SNRI good to tx: refractory depression, melancholy; more physical pain sx of depn; comorbid pain (duloxetine: DM periph neuropathy)
SNRI AE profile (which worse?) Venlafaxine > duloxetine
SNRI side fx GI (1st 3 wks); HTN (dose-dept (DBP) venlafaxine); withdrawal sim to SSRI
Use venlafaxine IR cautiously in pts with: HTN & cardiac dysfunction (use dulox or venla XR)
Mirtazapine (atypical) MOA unique: blocks central alpha-2 recs increasing NE & 5-HT; antag 5-HT2, 5-HT3 post-synaptic recs
Mirtazapine AE Somnolence, wt gain/inc appetite (used in cachectic pts), ortho hypotn
Bupropion MOA Weak reuptake inhibitor of NE and DA
Bupropion active metabolite: hydroxybupropion; has amphetamine properties (potent reuptake inhibitor of both NE and DA)
Bupropion AE Lower seizure threshold; vivid nightmares, delusions, psychosis
Do not give Bupropion to pts with: eating disorders (low electrolytes): seizure risk
Bupropion dosing Highest dose s/b usu 300; dose at early AM and noon (d/t insomnia, etc)
Atypical: good option for pts with sedation / fatigue / sexual dysfunction Bupropion
TCA MOA Block the reuptake of 5-HT and N; 1stGen: greater effect on 5-HT reuptake (Doxepin); 2ndGen: greater effect on NE reuptake (esp desipramine; clomipramine)
TCAs with best blockade of alpha- 1 & histamine- 1 recs: Amitriptyline & doxepin
TCA AE Anticholinergic (dry mouth, urin hesitancy, GERD; Cardiovascular (ortho hypotn, tachy, conduction, HTN); CNS (tremor, sedation, myoclonic twitch); wt gain; sexual dysfn
TCA dosing Start at low dose, titrate slowly, switch to less offensive agent; Bethanechol for anticholinergic AE; lethal in OD
MAOI MOA Block destruction of monoamines by presynaptic neuronal MAO; effect both central & periph; MAO-A = on NE & 5-HT; MAO-B = on phenylethylamine & DA
Irreversible MAO-I = Phenelzine & tranylcypromine
MAOI AE Wt gain; rash (selegiline); diet restrictn (liver, cheese, wine, yeast)
STAR-D General findings 6 wks necessary for pts achieve response; pts unable to tolerate med preferred switch; pts able to tolerate med preferred augmentation
STAR-D: Buproprion-SR: better results than buspirone
STAR-D Level 1 start citalopram
STAR-D Level 2 switch to: buprop SR, CBT, sert, venla XR; or augment w/bupro SR, buspar, CBT
STAR-D Level 2a (if CBT in level 2): switch to: buprop SR or venla XR
STAR-D Level 3 switch to mirtaz or nortrip; or augment w/lithium (poss T3 if bupro, sert, venla)
STAR-D Level 4 switch to tranylcypromine or mirtaz combo w/venla XR
Created by: Abarnard



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