s. saloojee- antipsychotics: when and what to prescribe
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ANTIPSYCHOTICSANTIPSYCHOTICS
WHEN AND WHAT TO PRESCRIBEWHEN AND WHAT TO PRESCRIBE
DR S. SALOOJEEDR S. SALOOJEE
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ANTI = AGAINST ANTI = AGAINST
ANTIPSYCHOTICANTIPSYCHOTIC
AGAINST PSYCHOSISAGAINST PSYCHOSIS
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PSYCHOSISPSYCHOSIS
DEFN : IMPAIRMENT IN REALITYDEFN : IMPAIRMENT IN REALITY
DSM 1V : SYMPTOM DEFINITIONDSM 1V : SYMPTOM DEFINITION
1.1. HALLUCINATIONSHALLUCINATIONS
2.2. DELUSIONSDELUSIONS
3.3. DISORGANIZED SPEECHDISORGANIZED SPEECH
4.4. DISORGANIZED BEHAVIOURDISORGANIZED BEHAVIOUR
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INDICATIONSINDICATIONS
ANYANY CONDITION WHERE THESECONDITION WHERE THESE
SYMPTOMS OCCURSYMPTOMS OCCUR
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PSYCHOTIC DISORDERSPSYCHOTIC DISORDERS
1.1. SchizophreniaSchizophrenia
2.2. SchizophreniformSchizophreniform disorderdisorder
3.3. Brief psychotic disorderBrief psychotic disorder
4.4. Delusional disorderDelusional disorder5.5. Psychotic disorder due to GMCPsychotic disorder due to GMC
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Natural History of SchizophreniaNatural History of SchizophreniaPremorbidProdromal Onset/
Deterioration
Residual/
Stable
Stages of Illness
HealthyWorsening
Severity ofSigns andSymptoms
Gestation/Birth 10 20 30 40 50Years
Lieberman J. Presented at: 154th APA Annual Meeting; May 5-10, 2001; New Orleans, La.
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MOOD DISORDERSMOOD DISORDERS
DEPRESSION WITH PSYCHOTICDEPRESSION WITH PSYCHOTICFEATURESFEATURES
Combine with an AntidepressantCombine with an Antidepressant
MANIA WITH PSYCHOTIC FEATURESMANIA WITH PSYCHOTIC FEATURES
Combine with a moodCombine with a mood stabiliserstabiliser
. AUGMENT ANTIDEPRESANT. AUGMENT ANTIDEPRESANTTreatment resistant depressionTreatment resistant depression
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Cognitive DisordersCognitive Disorders
1.1. DELIRIUMDELIRIUM
2.2. DEMENTIADEMENTIA
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FOR THE SIDE EFFECT OF THEFOR THE SIDE EFFECT OF THE
DRUGDRUG
1.1. SEDATIONSEDATION --------BehaviourBehaviour DisturbanceDisturbance
2.2. ANTI EMETICANTI EMETIC
3.3. HICCUPSHICCUPS
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Dawn of the Antipsychotic EraDawn of the Antipsychotic Era RevolutionisedRevolutionised treatmenttreatment
Held great promiseHeld great promise Extract fromExtract from Mental HospitalsMental HospitalsFebruary 1956February 1956
Many hospital psychiatrists are being pressuredMany hospital psychiatrists are being pressuredby relatives to useby relatives to use ChlopromazineChlopromazine where it didwhere it did
not seem to be indicated. To hold off relativesnot seem to be indicated. To hold off relatives
he would sayhe would sayIf you buy it, we will give itIf you buy it, we will give itbeing sure they would not dobeing sure they would not do so.Butso.But theythey
always obtained the money somehowalways obtained the money somehow
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AntipsychoticsAntipsychotics broadly classifiedbroadly classifiedinto two major classes :into two major classes :--
a) Typicala) Typicalantipsychoticsantipsychotics
b) Atypical (novel )b) Atypical (novel )antipsychoticsantipsychotics
other names :other names : NeurolepticsNeuroleptics
MajorMajor tranquiliserstranquilisers
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What makes an antipsychoticWhat makes an antipsychotic
Typical ?Typical ?
A) Its mechanism of actionA) Its mechanism of action
D2 receptor blockersD2 receptor blockers
b) Its site of actionb) Its site of action
Block Dopamine pathways nonBlock Dopamine pathways non
selectivelyselectively
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DOPAMINE PATHWAYSDOPAMINE PATHWAYS
1)1) MesolimbicMesolimbic
2)2) MesocorticalMesocortical
3)3) NigrostriatalNigrostriatal
4)4) TuberoinfundibularTuberoinfundibular
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MesolimbicMesolimbic reduction in positivereduction in positive
symptomssymptomsblockadeblockade
MesocorticalMesocortical
worsening of negativeworsening of negativeblockadeblockade symptoms. Cognitivesymptoms. Cognitive
deficitdeficit
NigrostriatalNigrostriatal Movement disordersMovement disorders
blockadeblockadeTuberoinfundibularTuberoinfundibular
hyperprolactinaemiahyperprolactinaemia
blocadeblocade
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a) Block Dopamine receptors ina) Block Dopamine receptors in
mesolimbicmesolimbic
but not in other pathways.but not in other pathways.
This has been partly achieved byThis has been partly achieved by
novelnovel
antipsychoticsantipsychotics..
B) No effects / minimal effects onB) No effects / minimal effects onotherother
receptorsreceptors
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GOALSGOALS
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ON CODEON CODE
1. Haloperidol1. Haloperidol--------SerenaceSerenace
2. Chlorpromazine2. Chlorpromazine------LargactilLargactil
3. Some clinics3. Some clinics------ClozapineClozapine------LeponexLeponex
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CHLORPROMAZINECHLORPROMAZINE
LargactilLargactil Typical AntipsychoticTypical Antipsychotic
Discovered in 1952Discovered in 1952
PricePriceR20R20R25 per monthR25 per month
FormulaFormula------tablets,syruptablets,syrup and injectionsand injections
D 2 Receptor blockerD 2 Receptor blocker
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PROPERTIESPROPERTIES
SedatingSedating High incidence ofHigh incidence ofanticholinergicanticholinergic sidesideeffectseffectsconstipation,blurredconstipation,blurred vision,urinaryvision,urinary
retention,cognitiveretention,cognitive effectseffects
Less EPS than HaloperidolLess EPS than Haloperidol
CardiotoxicCardiotoxic HepatotoxicHepatotoxicinduces liver enzymesinduces liver enzymes
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DOSEDOSE
Do not use injectionsDo not use injections------can causecan causeprecipitous drop in blood pressure andprecipitous drop in blood pressure andsevere tissue necrosissevere tissue necrosis
TabletsTablets------START LOWSTART LOW MaxMax600 mg daily600 mg daily
Monitor side effectsMonitor side effects
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LargactilLargactil vsvs SerenaceSerenace
YOUNGYOUNG FITFIT HEALTHYHEALTHY
AGGRESSIVEAGGRESSIVE PROMINENT BEHAVIOUR DISTURBANCEPROMINENT BEHAVIOUR DISTURBANCE
USE LARGACTILUSE LARGACTIL
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PROBLEMS WITH TYPICALSPROBLEMS WITH TYPICALS
Not always effectiveNot always effective------2525--30% of patients30% of patientsshow no improvementshow no improvement
Lots of side effectsLots of side effects
Not effective for negative symptomsNot effective for negative symptoms
No effect on cognitionNo effect on cognition
Poor compliancePoor complianceAffects workAffects work
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SIDE EFFECTSSIDE EFFECTS
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TypicalTypicalantipsychoticsantipsychotics
also block :also block :
11)) MuscarinicMuscarinic receptorsreceptors
2) Histaminic receptors2) Histaminic receptors
3)3) 1 ( alpha one ) receptors1 ( alpha one ) receptors
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MuscarinicMuscarinic
blockade causesblockade causes
urinary retention, constipation,urinary retention, constipation,
blurred vision, memory deficitblurred vision, memory deficit
Histaminic blockade causesHistaminic blockade causes
weight gain, sedationweight gain, sedation
1 blockade causes1 blockade causesPostural hypotension, reflexPostural hypotension, reflex
tachycardiatachycardia
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EXTRAPYRAMIDAL SIDE EFFECTSEXTRAPYRAMIDAL SIDE EFFECTS
ACUTE DYSTONIAACUTE DYSTONIA
PARKINSONISMPARKINSONISM
AKATHISIAAKATHISIA
TARDIVE DYSKINESIATARDIVE DYSKINESIA
NMSNMS
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ACUTE DYSTONIAACUTE DYSTONIA
YOUNG MALES PRONE TO ITYOUNG MALES PRONE TO IT DEVELOPS WITHIN HOURS OR DAYSDEVELOPS WITHIN HOURS OR DAYS
SPASM OF NECK .BACK ,EYE MUSCLESSPASM OF NECK .BACK ,EYE MUSCLES
POTENTIALLY FATALPOTENTIALLY FATAL
GIVE AKINETON 1 AMP. IMI OR IVIGIVE AKINETON 1 AMP. IMI OR IVI
CHANGE TYPICAL OR SWITCH TOCHANGE TYPICAL OR SWITCH TOATYPICALATYPICAL
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PARKINSONISMPARKINSONISM
Most common side effectMost common side effect5050--75%75% Onset within daysOnset within days
Triad of tremor ,Triad of tremor ,bradykinesiabradykinesia and rigidityand rigidity
Treated withTreated with anticholinergicanticholinergic medsmeds i.ei.eDisipalDisipal or oralor oral akinetonakineton
NEVER give prophylacticNEVER give prophylactic anticholinergicsanticholinergics
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AKATHISIAAKATHISIA
Prevalence 10%Prevalence 10% Onset usually within daysOnset usually within days
Treated with beta blockers orTreated with beta blockers orbenzodiazepinesbenzodiazepines
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TARDIVE DYSKINESIATARDIVE DYSKINESIA
Involuntary movementsInvoluntary movements ClassicallyClassically orooro--buccobucco--faciofacio--linguallingualmovementsmovements
Develops lateDevelops late Receptors supersensitiveReceptors supersensitive
Largely irreversibleLargely irreversible Switch toSwitch to clozapineclozapine
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NEUROLEPTIC MALIGNANTNEUROLEPTIC MALIGNANT
SYNDROMESYNDROME
IDIOSYNCRATICIDIOSYNCRATICANY TIMEANY TIME
ANY DOSEANY DOSE
TETRAD OF FEVER,RIGIDITY,AUTONOMICTETRAD OF FEVER,RIGIDITY,AUTONOMICHYPERAVTIVITY AND CONFUSIONHYPERAVTIVITY AND CONFUSION
MEDICAL EMERGENCYMEDICAL EMERGENCY SWITCH TO ATYPICALSSWITCH TO ATYPICALS
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So it stayed forSo it stayed for4040
years!years!
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YOU CAN REFERYOU CAN REFER
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WHEN TO REFERWHEN TO REFER
NON RESPONDERSNON RESPONDERS SENSITIVE TO EPSSENSITIVE TO EPS
PROMINENT NEGATIVE SYMPTOMSPROMINENT NEGATIVE SYMPTOMS
SEVERE DEPRESSIONSEVERE DEPRESSION
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Early warning signsEarly warning signs
WorriedWorried RestlessRestless
IrritableIrritable
InsomniaInsomnia
ParanoiaParanoia
Social withdrawalSocial withdrawal Substance abuse pattern changeSubstance abuse pattern change
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What to doWhat to do
Ensure complianceEnsure compliance Exclude substancesExclude substances
Exclude GMCExclude GMC
Increase doseIncrease dose
Switch to another typicalSwitch to another typical
Refer for atypicalRefer for atypical
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19701970ss LeponexLeponex
19941994 RisperdalRisperdal 19961996 OlanzapineOlanzapine
20002000 SeroquelSeroquel
20022002 GeodonGeodon
20032003 SolianSolian
20062006AbilifyAbilify
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Definition of AtypicalDefinition of Atypical
Clinical distinctionClinical distinction Minimal risk of EPSMinimal risk of EPS? Dose related phenomenon? Dose related phenomenon
Chemical DistinctionChemical Distinction Transient increaseTransient increaseinin prolactinprolactin levelslevels
Serotonin antagonismSerotonin antagonism
MesolimbicMesolimbic // MesocorticalMesocortical specificityspecificityA measure of dissociation at the receptorA measure of dissociation at the receptor
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CLOZAPINECLOZAPINE
PROBLEMSPROBLEMSAGRANULOCYTOSISAGRANULOCYTOSIS
EXCESSIVE SALIVATIONEXCESSIVE SALIVATION
SEDATIONSEDATION
SEIZURES AT HIGH DOSESSEIZURES AT HIGH DOSES
WEIGHT GAINWEIGHT GAIN METABOLIC SYNDROMEMETABOLIC SYNDROME
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Evidence of atypical antipsychotics superiorEvidence of atypical antipsychotics superiorefficacy to conventional antipsychotics hasefficacy to conventional antipsychotics hasbeen neither consistent nor robustbeen neither consistent nor robust
Need information from unbiased sources toNeed information from unbiased sources to
guide clinicians and policy makersguide clinicians and policy makers
Precedents from other fields in addressingPrecedents from other fields in addressing
critical questionscritical questions Lack of longer term headLack of longer term head--toto--headhead
comparisons of atypical and conventionalcomparisons of atypical and conventional
antipsychoticsantipsychotics
CATIE=Clinical Antipsychotic Trials of Intervention Effectiveness.Stroup TS, et al. Schizophr Bull. 2003;29(1):15-31.
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AT THE END OF THIS LECTUREAT THE END OF THIS LECTUREYOU SHOULD BE ABLE TO :YOU SHOULD BE ABLE TO :
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1) Define a Typical antipsychotic1) Define a Typical antipsychotic2) Name the Dopamine pathways and2) Name the Dopamine pathways and
know whatknow what
effects Dopamine blockade thereeffects Dopamine blockade thereproducesproduces
3) Describe the presentation and3) Describe the presentation and
management ofmanagement of
thethe extrapyramidalextrapyramidal syndromessyndromes
4) Discuss the side effects of Typical4) Discuss the side effects of Typicalantipsychoticsantipsychotics
5) Name and know the core properties of5) Name and know the core properties of
the Typicalthe TypicalAntipsychoticsAntipsychotics on the EDLon the EDL
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WE SPEND MORE BUT WE HAVE LESSWE SPEND MORE BUT WE HAVE LESS
WE HAVE MORE DEGREES BUT WE HAVEWE HAVE MORE DEGREES BUT WE HAVELESS SENSELESS SENSE
WE HAVE MORE MEDICATIONS BUT LESSWE HAVE MORE MEDICATIONS BUT LESSWELLNESSWELLNESS