B7 Pharmacology Final Exam (Lectures
12-22)
DSM5 oCriteria ofor oMajor oDepressive oDisorder o- o1+ omaj odepr oeps ow/o ohx
oman/hypoman
- 5+ oSIGECAPS osx onearly oeveryday o2w oper ow/ ochange ofrom oprev ofunc olev
- MUST oimpair ofunc/cause osubst odistr
- 1 osx oMUST obe odepr omood/anhed
SIGECAPS osx oof oMDD o- o- oSuic oideation ow/ ow/o oplan; osuic oatt; orecur othoughts oof
odeath
- Interest o(loss oint/pleas oin oactivs; oanhed)
- Guilt o(inappr/excess, ofeeling oworthlessness)
- Energy odecr
- Conc odecr; odiff omaking odecis
- Appet och o(typ odecr, ochange o5% owt ofrom obasel)
- Psychomot oagit/retard
- Sleep oimpair o(typ oinsom obut omaybe ohypersom)
Pathophysiology oof oMDD o(Biogenic oAmine oHypothesis) o- oresults ofrom omonoam oNT odef
ocort+limb obrain oareas
- Dopa, o5-HT, oand/or oNE oneurotransm oabnorms o--> odecr ocort oresp oto oemo
oactiv o--> oaffective odysf+depr ow/ oimpair oserot oNT
- Noradr ofibs oproj ofrom oloc ocerul oto ocer ocort+dopa ofibs oinnerv onuc oaccumb oalso oreg
omood
- monoam odef o--> oupreg opostsynR
Monoamine oNT oNeuronal oRegulation o& oAntidepressant oMOA o- ointerf ow/ otransp
omols oinhib oNT oreup oincr oamts oin osynapse
Monoamine oSystem oFeedback o- oDO oNOT ofunc oindep
ie. omed oenh oNE otransm omay osec oalter o5-HT+Dopa oactiv o& o5-HT oknown oto oinhib
oNE+Dopa orel oin ocert obrain oareas
NE oSynthesis, oBinding, oReuptake o- o- otyramine oconv oto oNE, ostored oin ovesics/degr oby
oMAO
- binds opostsyn oalpha/beta oadrenR; obinds/agonizes opresyn oalpha2R oinhib oNE orel
- Recyc oback opresyn oby oNET otransp
Serotonin oSynthesis, oBinding, oReuptake o- o- otryp oconv oto o5HT
- Binds omany opostsyn/presynR o--> oactiv opresynR oto odecr oneur ofiring
- SERT otransp ofor oreup
Problems ow/ oMonoamine oHypothesis o- oantideps orap ochanging omonoam oconcs
ohave odelayed oonset oto oeffic o--> oeffs omaybe osec oto oalter oR odens/sensits oOR osec
osig oPW o(ie. oinositol osynth odisr oin obipol odisord)
Neurotropic oHypothesis oof oMDD o- oinfl+overexc o--> odecr oneuroplas+neur odiff
- n oGF o(ie. oBDNF obr-der oneurotroph ofac) oreg oneuron oplasticity, oresil, oneurogen
o(incr osyn oconns)
,B7 Pharmacology Final Exam (Lectures
12-22)
- depr oassoc ow/ odecr oBDNF o--> odecr oneurotroph osupp o(also oassoc ow/
oDM+other onon- oneuro/psych odis)
- sust oNE/5HT osig oincr oBDNF oexpr
- antideps oincr oneurogen+syn oconn ocort oareas o(ie. ohippocamp)
Altered oGlutamate oNeurotransmission oin oMDD o- ooverexcit oin ocert obrain oareas
Neuroendocrine oFactors oin oMDD o- ohypoT+low osex osters o(estrog oin omenop, otestos)
oassoc ow/ odepr
- neuroactive osteroids olike oprogest ometabolite oAllopregnanolone odef ocorrel ow/ oPPD
Goals oof oTreatment oin oDepression o- o- oac odepr osx oresol
- prev ofunc olev oreturn
- suic oprev
- fut odepr oeps o(recur/relapse) oprev
Nonpharmacologic oInterventions ofor oMDD o- o- oPsychother o= o**1st oLINE ofor omild-
mod** odepr, oaddit oeffs ow/ opharm other, omaybe ocost+resource oprohib
- ECT o= o**LAST oLINE** ofor orefrac oMDD
- Exercise o--> oincr oBDNF
**Use opharm other+CBT ofor omod-sev odepr**
Acne otreatment othat omay oExacerbate oDepression o- oIsotretinoin
- mon opsych osx oper oREMS oprogram oiPledge
CV oMeds othat omay oExacerbate oDepression o- o- oReserpine o= odepl osymp obiogen
oamines oNE+Dopa; oused ofor oHTN obut opulled ofrom omarket odue oto ofatigue, odecr oenerg,
osex odysf?
- ARBs
- BBs o= oclassically olinked oto odepr obut oevid osupps ojust ophys osx ofatigue+low oenerg
- CCBs
- Clonidine
- Methyldopa
CNS oAgents othat oMay oExacerbate oDepression o- o- oDeutetrabenazine o&
oTetrabenazine o= odepl osyn omonamines oby odecr ovesic opresyn oneur otransp; o**BBW
odepr+suicidality**
- Valbenazine
Hormonal oTherapy othat omay oExacerbate oDepression o- o- oGRH o& oOCPs o=
oprogest+estrog oalters oposs olink oto omonoam ooxid oactiv
- Steroids o(ie. oPrednis) o= oposs oassoc ow/ oinfl+HPA oaxis ochanges oof odepr
Immunologic oAgent othat omay oExacerbate oDepression o- oInterferons
,B7 Pharmacology Final Exam (Lectures
12-22)
Smoking oCessation oDrug othat omay oExacerbate oDepression o- oVarenicline
Line oof oPharmacotherapy ofor oMod-Sev oDepression o- oFIRST oLINE ow/ oantideps oin
otop o3 oclasses oRx omeds
3 oPhases o& oGoals oof oDepression oPharm oTreatment o- o- oAcute oph o(6-12w) o= osx
oremis/abs
- Cont o(next o4-9m oafter oremis) o= oresid osx oelim/relapse o(sx oret ow/in o6m) oprev
- Maint o(@least o12-36m) o= orecur o(sep odepr oep) oprev
Duration oof oPharmacotherapy ofor oDepression o- opt-dep obased oon o# opast odepr oeps
Classes oof oAntidepressants o- o- oSSRIs
- SNRIs o(newer ogen o& oTCA)
- Atypical oAntideps
- MAOIs
Examples oof oSSRIs o- o- oCitalopram
- Escitalopram
- Fluoxetine
- Fluvoxamine
- Paroxetine
- Sertraline
Examples oof oNewer oGeneration oSNRIs o- o- oDesvenlafaxine
- Duloxetine
- Venlafaxine
- Levomilnacipran
Examples oof oTCAs o(class oof oSNRIs) o- o- oAmitriptyline
- Desipramine
- Doxepin
- Imipramine
- Nortriptyline
Examples oof oAtypical oAntidepressants o- o- oBupropion
- Nefazodone
- Trazodone
- Vilazodone
- Vortioxetine
- Mirtazapine
Examples oof oMAOIs o- o- oPhenelzine
- Selegiline
, B7 Pharmacology Final Exam (Lectures
12-22)
- Tranylcypromine
- Isocarboxazid
General oMOA oof oTCAs o- oblock oreuptake oboth oserot+NE o@ oSERT+NET obut
**nonspec+promisc** o@ oother orec osites
- block oserot oreup o& oincr osyn oconc
- cont ouse o--> oincr osyn oserot oconc odownreg opresyn oautoR+incr oraphe oneur ofiring orate
General oMOA oof oSNRIs o- oblock oserot+NE oreup obut o**don't oadditionally oblock oother oR
olike oTCA**
- cont ouse o--> oincr osyn oserot oconc odownreg opresyn oautoR+incr oraphe oneur ofiring orate
General oMOA oof oSSRIs o- oinhib oonly oserot oreup oon o5HT oterms
- cont ouse o--> oincr osyn oserot oconc odownreg opresyn oautoR+incr oraphe oneur ofiring orate
General oMOA oof oMAOIs o- oirrev obind oMAO omit ometab oserot+NE o--> oinhib oNE,
oserot, oDopa odegr
General oMOA oof oNSRIs o- oNE-sel oreup oinhibs oNOT oyet odev ofor odepr otreatment obut
ostim oAtomoxetine oknown oas oNSRI
NE o& oSerotonin oUptake oInhibition oby oSSRIs, oSNRIs, oTCAs o- o- oSSRI oFluox o= ono
oNE ouptake oinhib, o**only ohigh oserot ouptake oinhib**
- SNRI oVenlaf o= osome oNE oreup oinhib, ohigh oserot oreup oinhib
- SNRI oDulox o= ohigh oNE oreup oinhib, ohigh oserot oreup oinhib
- TCA oImipr o= ohigh oNE oreup oinhib, omod-high oserot oreup oinhib
- TCA oNortrip o= ohigh oNE oreup oinhib, osome oserot oinhib
Antidepressant oClass oEffects o- o- oequiv oeffic owhen oused o@ ocomp odoses oso oinit ochoice
ois oempiric o(NOT oa osingle orec o1st oline oagent)
- Facs oto oconsid o= opt oresp ohx, ofam oAD oresp ohx, oconcur omed oilln+meds, opres osx
o(ie. oinsom ovs ohypersom), odrug-drug oint opot, oAEs, opt opref, omed ocost
- **BBW oon oall oADs o= osuic othoughts+behav**, oNOT onecessarily oincr osuic oaction;
oincr orisk ochild, oadols, oYAs o<24y/o o& odecr orisk o>65y/o; omon oall opts
- **CAUTION oin obipol odisord-rel odepr ob/c omay ocause oswitch oto omanic obehav ow/o
ohaving omood-stab oon oboard**
Antidepressant oResponse o- o- omod-sev odepr o--> obenef odeps oon osev; omore osev
odepr, ogreater olikely obenefits; oprob oineff ofor omild odepr
- Find oeffect oag o= opt-spec; ofailure oto oresp oto o1 oAD oclass/1 oAD ow/in oclass oDOES
oNOT opred ofailed oresp oto oanother oclass/another oagent oin osame oclass
- Strats ofor opoor oresp o= oswitch ovs oaugm
12-22)
DSM5 oCriteria ofor oMajor oDepressive oDisorder o- o1+ omaj odepr oeps ow/o ohx
oman/hypoman
- 5+ oSIGECAPS osx onearly oeveryday o2w oper ow/ ochange ofrom oprev ofunc olev
- MUST oimpair ofunc/cause osubst odistr
- 1 osx oMUST obe odepr omood/anhed
SIGECAPS osx oof oMDD o- o- oSuic oideation ow/ ow/o oplan; osuic oatt; orecur othoughts oof
odeath
- Interest o(loss oint/pleas oin oactivs; oanhed)
- Guilt o(inappr/excess, ofeeling oworthlessness)
- Energy odecr
- Conc odecr; odiff omaking odecis
- Appet och o(typ odecr, ochange o5% owt ofrom obasel)
- Psychomot oagit/retard
- Sleep oimpair o(typ oinsom obut omaybe ohypersom)
Pathophysiology oof oMDD o(Biogenic oAmine oHypothesis) o- oresults ofrom omonoam oNT odef
ocort+limb obrain oareas
- Dopa, o5-HT, oand/or oNE oneurotransm oabnorms o--> odecr ocort oresp oto oemo
oactiv o--> oaffective odysf+depr ow/ oimpair oserot oNT
- Noradr ofibs oproj ofrom oloc ocerul oto ocer ocort+dopa ofibs oinnerv onuc oaccumb oalso oreg
omood
- monoam odef o--> oupreg opostsynR
Monoamine oNT oNeuronal oRegulation o& oAntidepressant oMOA o- ointerf ow/ otransp
omols oinhib oNT oreup oincr oamts oin osynapse
Monoamine oSystem oFeedback o- oDO oNOT ofunc oindep
ie. omed oenh oNE otransm omay osec oalter o5-HT+Dopa oactiv o& o5-HT oknown oto oinhib
oNE+Dopa orel oin ocert obrain oareas
NE oSynthesis, oBinding, oReuptake o- o- otyramine oconv oto oNE, ostored oin ovesics/degr oby
oMAO
- binds opostsyn oalpha/beta oadrenR; obinds/agonizes opresyn oalpha2R oinhib oNE orel
- Recyc oback opresyn oby oNET otransp
Serotonin oSynthesis, oBinding, oReuptake o- o- otryp oconv oto o5HT
- Binds omany opostsyn/presynR o--> oactiv opresynR oto odecr oneur ofiring
- SERT otransp ofor oreup
Problems ow/ oMonoamine oHypothesis o- oantideps orap ochanging omonoam oconcs
ohave odelayed oonset oto oeffic o--> oeffs omaybe osec oto oalter oR odens/sensits oOR osec
osig oPW o(ie. oinositol osynth odisr oin obipol odisord)
Neurotropic oHypothesis oof oMDD o- oinfl+overexc o--> odecr oneuroplas+neur odiff
- n oGF o(ie. oBDNF obr-der oneurotroph ofac) oreg oneuron oplasticity, oresil, oneurogen
o(incr osyn oconns)
,B7 Pharmacology Final Exam (Lectures
12-22)
- depr oassoc ow/ odecr oBDNF o--> odecr oneurotroph osupp o(also oassoc ow/
oDM+other onon- oneuro/psych odis)
- sust oNE/5HT osig oincr oBDNF oexpr
- antideps oincr oneurogen+syn oconn ocort oareas o(ie. ohippocamp)
Altered oGlutamate oNeurotransmission oin oMDD o- ooverexcit oin ocert obrain oareas
Neuroendocrine oFactors oin oMDD o- ohypoT+low osex osters o(estrog oin omenop, otestos)
oassoc ow/ odepr
- neuroactive osteroids olike oprogest ometabolite oAllopregnanolone odef ocorrel ow/ oPPD
Goals oof oTreatment oin oDepression o- o- oac odepr osx oresol
- prev ofunc olev oreturn
- suic oprev
- fut odepr oeps o(recur/relapse) oprev
Nonpharmacologic oInterventions ofor oMDD o- o- oPsychother o= o**1st oLINE ofor omild-
mod** odepr, oaddit oeffs ow/ opharm other, omaybe ocost+resource oprohib
- ECT o= o**LAST oLINE** ofor orefrac oMDD
- Exercise o--> oincr oBDNF
**Use opharm other+CBT ofor omod-sev odepr**
Acne otreatment othat omay oExacerbate oDepression o- oIsotretinoin
- mon opsych osx oper oREMS oprogram oiPledge
CV oMeds othat omay oExacerbate oDepression o- o- oReserpine o= odepl osymp obiogen
oamines oNE+Dopa; oused ofor oHTN obut opulled ofrom omarket odue oto ofatigue, odecr oenerg,
osex odysf?
- ARBs
- BBs o= oclassically olinked oto odepr obut oevid osupps ojust ophys osx ofatigue+low oenerg
- CCBs
- Clonidine
- Methyldopa
CNS oAgents othat oMay oExacerbate oDepression o- o- oDeutetrabenazine o&
oTetrabenazine o= odepl osyn omonamines oby odecr ovesic opresyn oneur otransp; o**BBW
odepr+suicidality**
- Valbenazine
Hormonal oTherapy othat omay oExacerbate oDepression o- o- oGRH o& oOCPs o=
oprogest+estrog oalters oposs olink oto omonoam ooxid oactiv
- Steroids o(ie. oPrednis) o= oposs oassoc ow/ oinfl+HPA oaxis ochanges oof odepr
Immunologic oAgent othat omay oExacerbate oDepression o- oInterferons
,B7 Pharmacology Final Exam (Lectures
12-22)
Smoking oCessation oDrug othat omay oExacerbate oDepression o- oVarenicline
Line oof oPharmacotherapy ofor oMod-Sev oDepression o- oFIRST oLINE ow/ oantideps oin
otop o3 oclasses oRx omeds
3 oPhases o& oGoals oof oDepression oPharm oTreatment o- o- oAcute oph o(6-12w) o= osx
oremis/abs
- Cont o(next o4-9m oafter oremis) o= oresid osx oelim/relapse o(sx oret ow/in o6m) oprev
- Maint o(@least o12-36m) o= orecur o(sep odepr oep) oprev
Duration oof oPharmacotherapy ofor oDepression o- opt-dep obased oon o# opast odepr oeps
Classes oof oAntidepressants o- o- oSSRIs
- SNRIs o(newer ogen o& oTCA)
- Atypical oAntideps
- MAOIs
Examples oof oSSRIs o- o- oCitalopram
- Escitalopram
- Fluoxetine
- Fluvoxamine
- Paroxetine
- Sertraline
Examples oof oNewer oGeneration oSNRIs o- o- oDesvenlafaxine
- Duloxetine
- Venlafaxine
- Levomilnacipran
Examples oof oTCAs o(class oof oSNRIs) o- o- oAmitriptyline
- Desipramine
- Doxepin
- Imipramine
- Nortriptyline
Examples oof oAtypical oAntidepressants o- o- oBupropion
- Nefazodone
- Trazodone
- Vilazodone
- Vortioxetine
- Mirtazapine
Examples oof oMAOIs o- o- oPhenelzine
- Selegiline
, B7 Pharmacology Final Exam (Lectures
12-22)
- Tranylcypromine
- Isocarboxazid
General oMOA oof oTCAs o- oblock oreuptake oboth oserot+NE o@ oSERT+NET obut
**nonspec+promisc** o@ oother orec osites
- block oserot oreup o& oincr osyn oconc
- cont ouse o--> oincr osyn oserot oconc odownreg opresyn oautoR+incr oraphe oneur ofiring orate
General oMOA oof oSNRIs o- oblock oserot+NE oreup obut o**don't oadditionally oblock oother oR
olike oTCA**
- cont ouse o--> oincr osyn oserot oconc odownreg opresyn oautoR+incr oraphe oneur ofiring orate
General oMOA oof oSSRIs o- oinhib oonly oserot oreup oon o5HT oterms
- cont ouse o--> oincr osyn oserot oconc odownreg opresyn oautoR+incr oraphe oneur ofiring orate
General oMOA oof oMAOIs o- oirrev obind oMAO omit ometab oserot+NE o--> oinhib oNE,
oserot, oDopa odegr
General oMOA oof oNSRIs o- oNE-sel oreup oinhibs oNOT oyet odev ofor odepr otreatment obut
ostim oAtomoxetine oknown oas oNSRI
NE o& oSerotonin oUptake oInhibition oby oSSRIs, oSNRIs, oTCAs o- o- oSSRI oFluox o= ono
oNE ouptake oinhib, o**only ohigh oserot ouptake oinhib**
- SNRI oVenlaf o= osome oNE oreup oinhib, ohigh oserot oreup oinhib
- SNRI oDulox o= ohigh oNE oreup oinhib, ohigh oserot oreup oinhib
- TCA oImipr o= ohigh oNE oreup oinhib, omod-high oserot oreup oinhib
- TCA oNortrip o= ohigh oNE oreup oinhib, osome oserot oinhib
Antidepressant oClass oEffects o- o- oequiv oeffic owhen oused o@ ocomp odoses oso oinit ochoice
ois oempiric o(NOT oa osingle orec o1st oline oagent)
- Facs oto oconsid o= opt oresp ohx, ofam oAD oresp ohx, oconcur omed oilln+meds, opres osx
o(ie. oinsom ovs ohypersom), odrug-drug oint opot, oAEs, opt opref, omed ocost
- **BBW oon oall oADs o= osuic othoughts+behav**, oNOT onecessarily oincr osuic oaction;
oincr orisk ochild, oadols, oYAs o<24y/o o& odecr orisk o>65y/o; omon oall opts
- **CAUTION oin obipol odisord-rel odepr ob/c omay ocause oswitch oto omanic obehav ow/o
ohaving omood-stab oon oboard**
Antidepressant oResponse o- o- omod-sev odepr o--> obenef odeps oon osev; omore osev
odepr, ogreater olikely obenefits; oprob oineff ofor omild odepr
- Find oeffect oag o= opt-spec; ofailure oto oresp oto o1 oAD oclass/1 oAD ow/in oclass oDOES
oNOT opred ofailed oresp oto oanother oclass/another oagent oin osame oclass
- Strats ofor opoor oresp o= oswitch ovs oaugm
