S. Saloojee- Antipsychotics: When and What to Prescribe

8/3/2019 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

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S. Saloojee- Antipsychotics: When and What to Prescribe

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