AntidepressantsAntidepressants

Psychology 3506Psychology 3506

IntroductionIntroduction

Pretty obvious what they are forPretty obvious what they are forBut, what is depression?But, what is depression?Not just feeling downNot just feeling downMore about flat affectMore about flat affectLack of emotionLack of emotionSeems to be more common now than everSeems to be more common now than ever

What is depression?What is depression?

Basically major depressive disorder, and Basically major depressive disorder, and bipolar.bipolar.

http://www.mentalhealth.com/dis1/p21-md01.html

http://www.mentalhealth.com/dis1/p21-md02.html

IntroductionIntroduction

Seems to be related to the monoaminesSeems to be related to the monoamines5 HT, NE and DA5 HT, NE and DA5 HT especially5 HT especially

May not be the cause, but certainly plays a May not be the cause, but certainly plays a rolerole

Seems all the drugs that work for Seems all the drugs that work for depression do something at seretonin depression do something at seretonin synapsessynapses

A teeny bit of historyA teeny bit of history

MAOI were discovered by accident, well, MAOI were discovered by accident, well, their antidepressant qualities anywaytheir antidepressant qualities anyway

So were Tri cyclicsSo were Tri cyclicsThe new The new ‘‘second generationsecond generation’’

antidepressantsantidepressantsThe SSRIs reallyThe SSRIs reallyPROZAC!!!PROZAC!!!

LithiumLithium

AbsorptionAbsorption

Similar for all three typesSimilar for all three typesMost destroyed by first pass metabolismMost destroyed by first pass metabolismOne to three hours for peak blood One to three hours for peak blood

concentrationconcentrationLonger with SSRIsLonger with SSRIsLi is poison!!Li is poison!!

Plus, a TI of like 3Plus, a TI of like 3carefulcareful

Distribution and excretionDistribution and excretion

Crosses all barriersCrosses all barriersMAOI have short half lifeMAOI have short half lifeTCA longer, almost 24 hrTCA longer, almost 24 hrSSRI 15 – 20 hrSSRI 15 – 20 hr

Except fluoxetineExcept fluoxetine6 day half life6 day half lifeNorfluoxetine, 16 days!!!!!!!!!Norfluoxetine, 16 days!!!!!!!!!

NeurophysiologyNeurophysiology

MAOI obviousMAOI obviousTCA stop reuptake of monoaminesTCA stop reuptake of monoaminesSSRI obviousSSRI obviousThese effects are immediate, but the These effects are immediate, but the

antidepressant effect is not, can take days antidepressant effect is not, can take days or weeks evenor weeks evenHmmmmmmmmmHmmmmmmmmm

How the hell does Li work?How the hell does Li work?

LithiumLithium

Some ideas include…..Some ideas include…..Magic….Magic….Altering GABAAltering GABAAttenuating GlutamateAttenuating Glutamate

Valproate works this way, so maybe….Valproate works this way, so maybe….

Affecting NO signaling pathwayAffecting NO signaling pathway Super dangerous as notedSuper dangerous as noted

.4 mmol/L concentration needed, about 1.2 can do .4 mmol/L concentration needed, about 1.2 can do you in, but, you might need this much for the you in, but, you might need this much for the mood stabilizing effects…..mood stabilizing effects…..

EffectsEffects

ACh effects (MZOI, TCA)ACh effects (MZOI, TCA)Dry mouthDry mouthConstipationConstipationDizzinessDizziness Irregular heartbeatIrregular heartbeatBlurred visionBlurred visionRinging earsRinging ears

EffectsEffects

SSRISSRINauseaNauseaNervousnessNervousnessHeadache Headache InsomniaInsomnia ‘‘Serotonin syndromeSerotonin syndrome’’

MAOI block MOAMAOI block MOAUmm, you need that to digest certain things, Umm, you need that to digest certain things,

so...so...

Sleep effectsSleep effects

TCAs can actually be used as sleeping TCAs can actually be used as sleeping pillspillsDonDon’’t overdo it…..t overdo it…..

Some SSRIs affect REM, some do notSome SSRIs affect REM, some do notMay actually be an antidepressant effectMay actually be an antidepressant effectFluoxetine seems to make dreams more Fluoxetine seems to make dreams more

vivid.vivid.

More effectsMore effects

No euphoriaNo euphoriaNo real No real ‘‘likingliking’’May be some cognitive effects, especially May be some cognitive effects, especially

TCATCAPersonality cosmetic??Personality cosmetic??

Tolerance and withdrawalTolerance and withdrawal

Both side effects and main effects show Both side effects and main effects show tolerancetolerance

Withdrawal can happen..Withdrawal can happen..AgitationAgitationNervousnessNervousnessChills Chills Muscle achesMuscle aches

Easier to keep people on SSRIsEasier to keep people on SSRIs

Bad StuffBad Stuff

‘‘male sexual functioningmale sexual functioning’’AhemAhem

Seems that there are no effects on Seems that there are no effects on fetuses, but, nasty side effects in lab fetuses, but, nasty side effects in lab animals, so, if you are pregnant, you animals, so, if you are pregnant, you should probably lay off the should probably lay off the antidepressantsantidepressants

ODOD