Biological Therapies

SSRIs

FluoxetineFluvoxamineParoxetineCitalopramSertralineescitalopram

SSRIs

Share no molecular featuresHalf life:20 hours&3daysHepatic metabolismSpecific activity in the inhibition of serotonin

reuptakeNo activity on other receptorsOccurring 90% of clinical response at the

starting dose

SSRIsTherapeutic Indications

DepressionAnxiety dis.Eating dis.PMSPremature

ejaculation

ParaphiliasADHDAutistic dis.chronic pain

syndromes.Psychosomatic

conditions

SSRIs Adverse Effects

Sexual dysfunctionGI effectsHeadacheCNS effectsAntichoinergic effectsHematologic effectsElectrolyte and glucose disturbancesEndocrine and allergic reactions

Serotonin syndrome

HyperthermiashiveringDiarrheaAgitationHyperreflexia

MyoclonusSeizuresRigidityDeliriumcoma

SSRI withdrawal

DizzinessWeaknessNauseaHeadacheRebound depressionAnxietyInsomniaPoor concentration

SSRIs

Drug-drug interactions

Dosage and administration

TCAs

Tertiary amines:

Imipramine

Amitriptyline

Trimipramine

Doxepine

Clomipramine

Secondary amines:

Desipramine

Nortriptyline

ProtriptylineTetracyclic drugs:

Maprotiline

Amoxapine

TCAs:

Half life :10-70h(longer HL in Nortriptyline,Maprotiline)

Hepatic metabolismBlocking of reuptake of serotonin and NEAntagonism of muscarinic,H1,alfa1,2Type A antiarrhytmic effects40-fold difference in plasma concentrations in

different persons

TCAsTherapeutic Indications

MDDPanic disorder with AgoraphobiaGADOCDEating dis.Pain dis.Sleep dis.

TCAsAdverse Effects

Psychiatric effectsAnticholinergic effectsSedationAutonomic effectsCardiac effectsNeurological effectsAllergic and hematological effectsWeight gain

TCAsDrug – Drug Interactions

AntihypertensivesAntipsychoticsCNS depressantsSympathomimeticsOCPsSSRIsLithiumPrimidonAscorbic Acid

MAOIs

PhenelzineIsocarboxazidTranylcypromineSelegiline

MAOIsTherapeutic Indications

Panic disorder with agoraphobiaSocial phobiaPTSDAtypical depressionEating dis.Pain dis.

MAOIsAdverse Reactions

Or HTNInsomniaWeight gainEdemaSexual dysfunctionHypertensive crisisparesthesia.,myoclonus,muscle pain

Tyramine-Rich Foods

CheeseFishSausagePatesMortadellabanana

drugs to be avoided

AntiasthmaticsAntihypertensivesBuspironeLevodopaOpioidsSympathomimeticsSSRIsClomipramine

Mood Stabilizers

LithiumSodium ValproateCarbamazepineLamotrigineTopiramateGabapentinCalcium Channel Inhibitors

lithium

No binding to plasma proteinsNo metabolismSlow crossing BBBHalf- life : 20 hoursDecreasing of renal clearance in renal

insufficiency and puerperium / increasing during pregnancy

Lithiumtherapeutic indications

Bipolar mood disorderSchizophrenia/schizoaffective disordersMDDAggressionPMSBulimiaBinge drinkingBPDOCDPTSDTrichotilomania

Lithiummaintenance treatment

After the second episode of BMD1 After the first episode in :

1. Adolescents

2. High suicide risk

3. Poor support systems

4. No percipitating factors

5. Sudden onset

6. First episode of mania

7. FH of BMD1

LITHIUMAdverse effects

Gastrointestinal effectsNeurological effectsRenal effectsCardiac effectsThyroid effectsDermatological effects

Lithium toxicityCoarse tremorDysarthriaAtaxiaGI symptomsCardiovascular changesRenal dysfunctionFasciculationsMyoclonusSeizurescoma

LITHIUMDrug interactions

DAsAnticonvulsantsThiazidsPotassium sparing

diureticsNSAIDsACEIsCalcium channel

inhibitors

Osmotic diureticsLoop diureticsXantinsCarbonic anhydrase

inhibitors

LithiumClinical Guidelines

Initial medical work upDosageSerum concentrationsDiscontinuationPatient education

Sodium valproate

Effects on GABA neurotransmitter system.Therapeutically effective at serum

concentrations above 50 -100 microgr/mlHalf-life : 8-17 hoursMaintaining effective plasma concentrations

with dosing 1 to 4 times a day

Sodium ValproateTherapeutic Indications

Bipolar 1Disorder (acute – prophylaxis )Schizoaffective DisorderBehavioral dyscontrol syndromesDementiaOrganic brain diseasesTBIOther mental disorders

Sodium Valproate Adverse Reactions

GI effectsSedationAtaxiaDysarthriaTremorWeight gainHair loss

Elevation of liver transaminases

ThrombocytopeniaPlatelet dysfunctionHyponatremiaHepatotoxicityPancratitisPCO

Sodium ValproateDrug interactions

Lithium CarbamazepinAntidepressantsSDAsDAsPhenytoinPhenobarbitalBZDs

Sodium ValproateAdministration

R/O liver and pancreatic diseaseDose on the first day : 250 mgplasma concentrations : 50-100 mg/mlDaily dose : 1200-1500mgMood-stabilizing effects appear between 5-15

days after initiation

Carbamazepine

Steady-state levels in 2-4 days on a steady dosage

Half-life : 12-17 h after 1 month of administration

Metabolized in liverdecreasing synoptic transmission Reduction of currents through NMDA

channelsAntagonism of adenosine A1 receptors

Carbamazepine Therapeutic Indications

Bipolar disorder (manic-depressive episodes)Schizophrenia and schizoaffective disorderImpulse-control dis.PTSDAlcohol and BZD withdrawal

CarbamazepineAdverse Reactions

Blood DyscrasiasHepatitisExfoliative dermatitisGI EffectsCNS EffectsCardiac EffectsHyponatremia

CarbamazepineDrug Interactions

SSRIsAnti psychoticsCimetidineErythromycinIsoniazideKetoconazoleVerapamilallopurinol

OCPTCAsNa-valproateBupropionMAOIsClomipraminePrimidonePhenytoin

CarbamazepineTreatment

CBC,LFT,ECG,Serum ElectrolytesInitiate with 200mg to 600-1200mgAnticonvulsant Blood Concentration : 4-

12microgr/mlLaboratory

Monitoring :CBC ,Billirubin,LFT,CBZ Level

CarbamazepineTreatment Discontinuation

WBC<3000/mm3Erythrocyte Count < 4000000/mm3PMN<1500/mm3HCT <32%HB<11gr/100mlReticulocyte Count<0.3 %Serum Iron Concentration,150mg/100ml