Ch 7: Antidepressant Medications

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THEORIES OF ANTIDEPRESSANT ACTION

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•AmineTheory

•ReupTakeInhibition

•DownregulationTheory

•Cellular/MolecularTheory

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AmineTheory

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•amine hypothesis proposed that people who suffered from depression did not have enough amines, particularly Norepinephrine (NE), in their synapses, and if you could increase the NE, then they would not be depressed

•does not explain lag time in treatment response

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ReupTakeInhibition

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•proposed that the transporter molecule attaches to the NE neurotransmitter and sends it back in the cell after it binds to receptors
•enzymes store it in synaptic vesicles so it can be released again, almost like a recycling service
•does not explain lag time

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DownregulationTheory

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•proposed that there are two mechanisms at work: increase to normal the level of neurotransmitter released into the synapse(reuptake inhibition), and downregulation of receptors to a normal level of responsiveness(to adapt to the increased levels of neurotransmitter)
•helps to explain the 2-4 week lag time of antidepressants to start

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Cellular/MolecularTheory:

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• meta-theory that encompasses and transcends all prior theories
•proposes that cell goes through many changes after an antidepressant agent is introduced, and the increase in cell nutrients is a significant dimension to change in the system
•cell nutrients are interestingly also “fed”through regular physical exercise

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TYPES OF ANTIDEPRESSANTS

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1)MAOInhibitors
2)Tricyclic Antidepressants (TCAs)
3)Selective Serotonin Reuptake Inhibitors (SSRIs)
4)Atypical Antidepressants

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MAOIs 1

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•initiallyintroducedasamajortranquilizer
•firstgenerationMAOI(Iproniazid)fellintodisfavorbecauseoflivertoxicity
•lesstoxicMAOIs(Marplan,Nardil)continuetoposephysicalproblems
•MAOIsarenotorganspecific,anddrugimpactotherareasofthebody
•sideeffectsofdrugaremoresevereandmorefrequentthanthoseofotherantidepressants
•WorkdifferentlythanSSRIsorSNRIs:TheyinhibitMAOI,theenzymethatbreaksdownneurotransmittersandRendersthemineffective

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MAOIs 2

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•mostdangeroussideeffectsoftraditionalMAOIsistyramineintolerance(liverdamage)
•ifMAOIsarediscontinued,clientshouldmaintaindietaryrestrictionsfortwoweeks
•MAOIsareusedtotreatdepressionthathasbeenresistanttotreatmentwithothertypesofantidepressants
•ContraindicationsforMAOItherapy:historyofliverdisease,congestiveheartfailure,recreationaldruguse/abuse/dependence,hypertension,oruncontrollabletyramineconsumption;patientsunlikelytoabidebytheexpecteddietaryrestrictions

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MAOIs

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•MAOIs are also used in the treatment of severe anxiety states and have positive effects on the eating behavior and mood of patients with bulimia and anorexia nervosa
•Most common side effects of MAOI use include changes in blood pressure, sleep disturbances, insomnia and over eating especially of carbohydrates which typically leads to excessive weight gain.
•Used as a last resort drug for clients who do not respond well to other medications

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Examples of MAOIs

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Front 11

Examples of Foods High in Tyramine Content to Avoid When Taking MAOIs

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•Cheeses (cream cheese, such as the common Philadelphia brand, and cottage cheese are safe)
*Chicken liver and beef live
*Yeast preparations (avoid brewer’s yeast, and powdered and caked yeast as sold in health food stores)
*Broad beans and fava beans
*Herring
*Beer, sherry, ale, red wine, liqueurs
*Canned figs
*Protein extracts (such as soup cubes and commercial gravies)

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Activating vs. Sedating Anti-Depressants

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•Antidepressants are prescribed depending on several factors: psychiatric symptomology, prior drug history, past experience with depression, state of routine physical activity
•Selection of a particular anti-depressant is evaluated with regard to reported and stated level of arousal

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Activating vs. Sedating Anti-Depressants

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Activating: Prozac, Wellbutrin, and Zoloft

Sedating: Paxil, Luvox, and Remeron

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Common Side Effects of MAO Inhibitors

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•Orthostatic hypertension (a drop in blood pressure that results in dizziness on standing)
•Nighttime insomnia, daytime sedation
•Headache
•Muscle cramps
•Weight gain
•Difficulty urinating
•Tyramine intolerance

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TricyclicAntidepressants

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•amongthemostextensivelystudieddrugonthemarket
•TCAswereunexpectedlybornfromChlorpromazine,andarereferredtoasFirstGenerationAntidepressants
•drugwascreatedbecausedrugcompanieswereseekingcompoundswithfewersideeffectsandwithapplicationtootherdisorders
•TCAsbecamedrugofchoicefordepressionthroughthe1980suntilProzacwasintroducedin1988
•Inearly1980’s,a2ndgenerationTCAwasintriduced:Tazodone(Desyrel).Lesslikelytocausesexualsideeffectsbutmaycauseacondition(proapism)resultinginaprolongedpainfulerectioninmen.

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TricyclicAntidepressants

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•amongthemostextensivelystudieddrugonthemarket
•TCAswereunexpectedlybornfromChlorpromazine,andarereferredtoasFirstGenerationAntidepressants
•drugwascreatedbecausedrugcompanieswereseekingcompoundswithfewersideeffectsandwithapplicationtootherdisorders
•TCAsbecamedrugofchoicefordepressionthroughthe1980suntilProzacwasintroducedin1988
•Inearly1980’s,a2ndgenerationTCAwasintriduced:Tazodone(Desyrel).Lesslikelytocausesexualsideeffectsbutmaycauseacondition(proapism)resultinginaprolongedpainfulerectioninmen.

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TricyclicAntidepressants

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•primarymechanismofactionsinallTCAsisinhibitionofthereuptaketransmitters,NorepinephrineandSerotonin
•allTCAsblockreceptorsonacetycholine,histamine,andepinephrinewhichcausesmostofthesideeffects
•choiceofcorrectTCAisbasedonmatchingthedrugtotheclient’ssymptoms(Elavilismoresedating,Norpraminismorestimulating)
•keydrawbackstoTCAs:slowonsetofaction,unreliableeffectivenessfromclienttoclient,difficultsideeffects,highoverdosepotential
•Klonopin-Benzodiazapineoftenusedforitsmoodstimulatingproperties

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Example of Tricyclic Antidepressants and Common Dosage Ranges

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Common TCA Side Effects

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SelectiveSerotoninReuptakeInhibitors

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•ReferredtoasSecondGenerationAntidepressants
•treatmenteffectssimilartothoseofTCAswithoutasmanysideeffects
•TCAsaremolecularlysimilar,however,SSRIsareremarkedlydifferentinchemicalstructure
•ifclientsdon’trespondtooneTCA,itisunlikelytheywillrespondtoanother;differentwithSSRIswhereaftersomeexperimentation,anotherdrugwilllikelyprovidesomeoptimalrelief

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SelectiveSerotoninReuptakeInhibitors

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•primarymechanismofactionistheinhibitionofreuptakeofserotoninbackintotheneuron
•unlikeTCAs,SSRIshavefarfeweranticholinergicorantihistaminesideeffects
•majordifficultywithSSRIsisthecommonsideeffectofsexualdysfunction
•additionofWellbutrin(notanSSRI)increasesleveloftheNT(Dopamine)whichincreasessexualdesire
•roleofviolencewithSSRIs(ChurchofScientologywiththedrugProzac[1989],ColombineHighSchooltragedy[Paxel])

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Examples of SSRI Antidepressants and Common Daily Dosage Ranges

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Front 23

Common SSRI Side Effects

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Headache
Nausea
Nervousness
Diarrhea
Insomnia
Weight gain
Sexual dysfunction
Difficulty urinating

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Symptoms of Serotonin Withdrawal

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•Lethargy
•Fatigue
•Gastrointestinal (nausea, vomiting, diarrhea
•Paresthesias (numbness or tingling in extremities)
•Insomnia
•Agitation/anxiety

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AtypicalAntidepressants [Heterocyclics]

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Antidepressants
•drugshavebettersideeffectsprofile,andaremoresafethanMAOIsandTCAs
•appeartobeonlyaseffectiveasSSRIs

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Current Third-Generation Antidepressants

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Front 27

Summary of Antidepressant Medication Use

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•The incidence of depression dramatically increases from adolescents to early adulthood
–Average age of the onset is the late twenties, although the disorder may begin virtually at any time.
•Depression occurs in up to one in eight individuals over a lifetime making it one of the most prevalent of all medical conditions
•Treatment resistant depression:treatment non response has been variably defined but typically involves the persistence of significant depression for at least six weeks despite two or more appropriate medication treatments. There are four critical issues to consider:
–Appropriate diagnosis
–Drug adherence
–Adequate dose
–Adequate duration of treatment

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Summary of Antidepressant Medication Use 2

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•Incorrect diagnosis the most common cause for non-response to anti-depressants.
•Seasonal affective disorder (SAD) is a recurrent depressive illness that regularly coincides with particular seasons:
–Spring onset type (SOSAD) is usually more severe although less frequent and associated with a greater risk of suicide, hospitalization, and the need for somatic treatments (ECT).
–Fall onset type (FOSAD) is more common and results in less severe depressive moods and is typically managed on an outpatient basis, and there is less danger of suicide.

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Summary of Antidepressant Medication Use

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•Criteria for improvement with antidepressants:
–Watch for improvement in symtomotology
–Psychomotor agitation or retardation often improves first
–Concentration and increased capacity for interpersonal contact improves next
–Patients’ subjective sense of depression, anadonia and hopelessness improves towards the fourth to sixth week of treatment.
–Maintenance therapy for Major Depressive Disorder should be carefully watched to prevent a relapse back to prior episode.

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SSRIs and SNRIs

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•SSRIs
–Ease, relative lack of cardiotoxicity, single mechanism of action
–Sexual dysfunction, akathesia, CYP450, discontinuation syndrome, tramadol-seizures, Serotonin syndrome, headache, nausea, “flattening” of emotions
•SNRIs
–Minimal p450 interaction, good w/tx resistance, some evidence indicating more complete full remission
–Sexual dysfunction, akathesia, wide dose variability, discontinuation syndrome

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Medication Protocol Consultation for Antidepressant Use

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Front 32

Treatment Considerations: Adolescents

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•FDA Approved for depression:
–Citalopram (Celexa)
–Escitalopram (Lexapro)
–Fluoxetine (Prozac)
•TCA’s not effective for adolescents
•SNRIs less studied, however increasingly being used
•Assess for akathesia-highly correlated to suicidality

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Managing Adverse Effects

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•Akathesia “too much coffee feeling”
–Switch unless stellar response
–Add propranolol, benzodiazepines
–Decrease/slow down rate of dose
•Sexual Dysfunction
–Skip a dose
–Buproprion, buspirone, Viagra, Cialis
•Anticholinergic
–Slow down titration/decrease dose/change agent
–Comfort measures
•Drowsiness
–Change time of day, slow down titration

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Recommendations

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1.Start with easier medications first: fluoxetine (Prozac), citalopram (Celeza), Sertraline (Zoloft).
•Citalopram has fewer side effects and Interacts with fewer other medications
2.Partial response to an SSRI could mean:
a)May need other neurotramitter (norepinephrine, dopamine)
b)Dx is inacurate
c)Inadequate dose

3.0 response to several antidepressant medications could mean abuse of alcohol or other substances
4.Antidepressants take time to work: set expectation with clients
5.Inform client about types of side effects to expect (i.e. dry mouth, inability to reach orgasm, insomnia, sedation, weight gain, stomach upset).
6.Remind client that medication should not be stopped abruptly
7.Pregnant clients should be very cautious about taking antidepressants